首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1239184760455623313, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1239184752507408921, articleNumber=null, orderNo=null, doi=10.16155/j.0254-1793.2024-0227, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1712419200000, receivedDateStr=2024-04-07, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773374269832, onlineDateStr=2026-03-13, pubDate=1735574400000, pubDateStr=2024-12-31, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773374269832, onlineIssueDateStr=2026-03-13, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773374269832, creator=13701087609, updateTime=1773374269832, updator=13701087609, issue=Issue{id=1239184752507408921, tenantId=1146029695717560320, journalId=1205117023404326918, year='2024', volume='44', issue='12', pageStart='2011', pageEnd='2188', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1773374267937, creator=13701087609, updateTime=1773374446543, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1239185501702377864, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1239184752507408921, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1239185501702377865, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1239184752507408921, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2078, endPage=2087, ext={EN=ArticleExt(id=1239184761143489193, articleId=1239184760455623313, tenantId=1146029695717560320, journalId=1205117023404326918, language=EN, title=Research on related substances of salbutamol sulfate inhalation aerosol in national drug sampling and testing*, columnId=1206272757852074373, journalTitle=Chinese Journal of Pharmaceutical Analysis, columnName=Safety Monitoring, runingTitle=null, highlight=null, articleAbstract=
Objective:

To study the related substances in salbutamol sulfate inhalation aerosol during national drug sampling and testing, and to compare the impurity content and evaluate the quality between samples from various enterprises.

Methods:

HPLC external standard method was utilized to simultaneously determine the content of related substances A, B, C, D, E, F, G, H, I, J, N, and other unknown impurities in salbutamol sulfate inhalation aerosol. Thermo Synchronis C8 chromatography column (250 mm×4.6 mm, 5 μm) was used. Sodium heptane sulfonate solution-acetonitrile was used as the mobile phase. Linear gradient elution was performed and the flow rate was 1.0 mL·min-1. Column temperature was 40 ℃ and detection wavelength was 220 nm. Injection volume was 20 μL. The sources of impurities through forced degradation experiments were explored. Toxicity prediction software for impurity toxicity assessment was applied.

Results:

After method validation, the specificity of the method was good, and the separation degree between each impurity peak was greater than 1.5. RSDs of precision test were 0.30%-1.7%(n=6)；mass concentrations of linear range were from 0.050 to 5.000 μg·mL-1(r=0.999 9). Limit of quantitative was in the range of 0.025-0.200 μg·mL-1, limit of detection was in the range of 0.008-0.070 μg·mL-1. The repeatability RSD of raw materials was 0.80%-3.8%, and the recovery rate was 95.2%-104.8%. The repeatability RSD of inhaled aerosol was 1.2%-2.9%, and the recovery rate was 98.7%-102.8%. The forced degradation test showed that impurities D, F, I, J, and N were all degradation impurities. 110 batches of samples were checked and the results of the relevant substances met the regulations. In the samples of diverse enterprises, impurities C, D, F, and N were detected more frequently, while impurities E, G, and H were not detected. Impurity J was only detected in one batch. The predicted impurity D by QSAR software falls to ICH M7 (R2) level 2.

Conclusion:

The established method is sensitive and accurate, and can accurately quantify the content of related substances in salbutamol sulfate aerosol, providing effective technical support for systematic supervision. Further toxicity studies should be conducted on impurity D and reasonable limits should be established.

, correspAuthors=Xiang-mi PAN, Yu-wen XU, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Lian-yi ZHANG, Wen-xin LI, Tie-jun LI, Chong NIU, Shu-juan YANG, Wen-xin WANG, Yan-li DOU, Jing ZHENG, Xiang-mi PAN, Yu-wen XU), CN=ArticleExt(id=1239184770610032669, articleId=1239184760455623313, tenantId=1146029695717560320, journalId=1205117023404326918, language=CN, title=国家药品抽检中硫酸沙丁胺醇吸入气雾剂有关物质研究*, columnId=1206272758036623764, journalTitle=药物分析杂志, columnName=安全监测, runingTitle=null, highlight=null, articleAbstract=
目的：

对国家药品抽检品种硫酸沙丁胺醇吸入气雾剂的有关物质进行探索性研究，比较各企业样品之间含有杂质的情况，以评价药品质量。

方法：

采用HPLC外标法同时测定硫酸沙丁胺醇吸入气雾剂中有关物质A、B、C、D、E、F、G、H、I、J、N及其他未知杂质含量。采用Thermo Syncronis C8（250 mm×4.6 mm，5 μm）色谱柱；以庚烷磺酸钠溶液-乙腈为流动相，进行线性梯度洗脱；流速1.0 mL·min-1；柱温40 ℃；检测波长220 nm；进样体积20 μL。结合强制降解试验探讨杂质来源，并采用毒性预测软件进行杂质毒性评估。

结果：

经方法验证，方法专属性良好，各杂质峰之间分离度均>1.5；精密度试验的RSD为0.30%~1.7%（n=6）；线性范围在0.050~5.000 μg·mL-1（r=0.999 9）；定量限在0.025~0.200 μg·mL-1，检测限在0.008~0.070 μg·mL-1；原料药重复性的RSD为0.80%~3.8%，平均回收率95.2%~104.8%；吸入气雾剂重复性的RSD为1.2%~2.9%，回收率98.7%~102.8%。强制降解试验表明，杂质D、F、I、J、N均为降解杂质。对抽检的110批次样品进行检测，有关物质结果均符合规定。各企业样品中，杂质C、D、F、N检出频次较高，杂质E、G、H均未检出，杂质J仅检出1批次。其中杂质D的QSAR软件预测ICH M7（R2）分类为2级。

结论：

建立的方法灵敏准确，可准确地对硫酸沙丁胺醇气雾剂的有关物质含量进行定量测定，能为科学监管提供有效的技术支持。应对杂质D进行进一步的毒性研究，并确定合理的限度。

, correspAuthors=潘相蜜, 徐玉文, authorNote=null, correspAuthorsNote=
**潘相蜜　Tel：18668991066；E-mail：
徐玉文　Tel：13553158409；E-mail：
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=DJeHL3FDBjX/wuKJwFIAFg==, magXml=iITWM3fxCn62BIj3/dn3ww==, pdfUrl=null, pdf=iL3gR2V+zpLxd9+g8oKr4g==, pdfFileSize=2944183, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=LpkEDq2VOPqpEvo+RwxMRg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=qGeThkU6kzAi2MYG2z43cw==, mapNumber=null, authorCompany=null, fund=null, authors=

Tel：18853105319；E-mail：

, authorsList=张连义, 李文馨, 李铁军, 牛冲, 杨书娟, 王文心, 窦艳丽, 郑静, 潘相蜜, 徐玉文)}, authors=[Author(id=1239218777221558303, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=18853105319@163.com, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218777414496294, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218777221558303, language=EN, stringName=Lian-yi ZHANG, firstName=Lian-yi, middleName=null, lastName=ZHANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218777561296940, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218777221558303, language=CN, stringName=张连义, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101, bio={"content":"

Tel：18853105319；E-mail：

"}, bioImg=null, bioContent=

Tel：18853105319；E-mail：

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)])]), Author(id=1239218777695514674, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218777821343804, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218777695514674, language=EN, stringName=Wen-xin LI, firstName=Wen-xin, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218777926201410, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218777695514674, language=CN, stringName=李文馨, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)])]), Author(id=1239218778039447626, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218778114945103, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218778039447626, language=EN, stringName=Tie-jun LI, firstName=Tie-jun, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2.Shandong Jewim Pharmaceutical Co., Ltd., Taian 271000, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218778228191318, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218778039447626, language=CN, stringName=李铁军, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, address=2. 山东京卫制药有限公司，泰安 271000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776886013967, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=2., ext=[AuthorCompanyExt(id=1239218776894402574, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776886013967, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Shandong Jewim Pharmaceutical Co., Ltd., Taian 271000, China), AuthorCompanyExt(id=1239218776898596879, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776886013967, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. 山东京卫制药有限公司，泰安 271000)])]), Author(id=1239218778307883098, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218778425323621, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218778307883098, language=EN, stringName=Chong NIU, firstName=Chong, middleName=null, lastName=NIU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218778551152745, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218778307883098, language=CN, stringName=牛冲, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)])]), Author(id=1239218778630844527, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218778710536312, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218778630844527, language=EN, stringName=Shu-juan YANG, firstName=Shu-juan, middleName=null, lastName=YANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218778819588222, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218778630844527, language=CN, stringName=杨书娟, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)])]), Author(id=1239218779922690181, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218780094656652, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218779922690181, language=EN, stringName=Wen-xin WANG, firstName=Wen-xin, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218780207902866, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218779922690181, language=CN, stringName=王文心, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)])]), Author(id=1239218780325343387, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=6, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218780430200992, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218780325343387, language=EN, stringName=Yan-li DOU, firstName=Yan-li, middleName=null, lastName=DOU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218780539252903, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218780325343387, language=CN, stringName=窦艳丽, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)])]), Author(id=1239218780652499117, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=7, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1239218780786716849, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218780652499117, language=EN, stringName=Jing ZHENG, firstName=Jing, middleName=null, lastName=ZHENG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218780899963062, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218780652499117, language=CN, stringName=郑静, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)])]), Author(id=1239218781009014968, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=8, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=3402553714@qq.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1239218781101289661, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218781009014968, language=EN, stringName=Xiang-mi PAN, firstName=Xiang-mi, middleName=null, lastName=PAN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=3, **, address=3.The Fifth People’s Hospital of Jinan, Jinan 250022, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218781222924485, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218781009014968, language=CN, stringName=潘相蜜, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=3, **, address=3.济南市第五人民医院，济南 250022, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218777049591825, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=3., ext=[AuthorCompanyExt(id=1239218777066369045, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218777049591825, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.The Fifth People’s Hospital of Jinan, Jinan 250022, China), AuthorCompanyExt(id=1239218777083146263, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218777049591825, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.济南市第五人民医院，济南 250022)])]), Author(id=1239218781319393478, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, orderNo=9, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=13553158409@163.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1239218781432639693, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218781319393478, language=EN, stringName=Yu-wen XU, firstName=Yu-wen, middleName=null, lastName=XU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, 2, **, address=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China
2.Shandong Jewim Pharmaceutical Co., Ltd., Taian 271000, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1239218781545885904, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, authorId=1239218781319393478, language=CN, stringName=徐玉文, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, 2, **, address=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101
2. 山东京卫制药有限公司，泰安 271000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)]), AuthorCompany(id=1239218776886013967, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=2., ext=[AuthorCompanyExt(id=1239218776894402574, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776886013967, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Shandong Jewim Pharmaceutical Co., Ltd., Taian 271000, China), AuthorCompanyExt(id=1239218776898596879, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776886013967, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. 山东京卫制药有限公司，泰安 271000)])])], keywords=[Keyword(id=1239218781772378322, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=1, keyword=national drug sampling), Keyword(id=1239218781898207449, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=2, keyword=exploratory research), Keyword(id=1239218782019842268, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=3, keyword=salbutamol sulfate inhalation aerosol), Keyword(id=1239218782107922655, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=4, keyword=related substances), Keyword(id=1239218782233751780, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=5, keyword=source of impurities), Keyword(id=1239218782326026471, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=6, keyword=forced degradation test), Keyword(id=1239218782405718252, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=7, keyword=relative correction factor), Keyword(id=1239218782544130290, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=8, keyword=high performance liquid chromatography), Keyword(id=1239218782669959413, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, orderNo=9, keyword=quantitative structure-activity relationship), Keyword(id=1239218782783205624, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=1, keyword=国家药品抽检), Keyword(id=1239218782955172095, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=2, keyword=探索性研究), Keyword(id=1239218783085195522, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=3, keyword=硫酸沙丁胺醇吸入气雾剂), Keyword(id=1239218783198441734, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=4, keyword=有关物质), Keyword(id=1239218783290716426, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=5, keyword=杂质来源), Keyword(id=1239218783378796815, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=6, keyword=破坏试验), Keyword(id=1239218783487848723, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=7, keyword=相对校正因子), Keyword(id=1239218783567540502, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=8, keyword=高效液相色谱法), Keyword(id=1239218783684981018, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, orderNo=9, keyword=定量构效关系)], refs=[Reference(id=1239218786398695780, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2013, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=张雪梅, journalName=null, refType=null, unstructuredReference=张雪梅. 左旋硫酸沙丁胺醇肺部吸入给药的制剂与药效与作用研究[D]. 广州：华南理工大学，2013, articleTitle=左旋硫酸沙丁胺醇肺部吸入给药的制剂与药效与作用研究, refAbstract=null), Reference(id=1239218786461610342, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2013, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[1], rfOrder=1, authorNames=ZHANG XM, journalName=null, refType=null, unstructuredReference=ZHANG XM. The Study on Preparation and Pharmacodynamics of R-Salbutamol Sulfate for Pulmonary Inhalation[D]. Guangzhou：South China University of Technology，2013, articleTitle=The Study on Preparation and Pharmacodynamics of R-Salbutamol Sulfate for Pulmonary Inhalation, refAbstract=null), Reference(id=1239218786537107816, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2012, volume=73, issue=5, pageStart=543, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=2, authorNames=KHALE A, BAJAJ A, journalName=Indian J Pharm Sci, refType=null, unstructuredReference=KHALE A，BAJAJ A. Formulation and development of metered dose inhalations of salbutamol in solution form[J]. Indian J Pharm Sci，2012，73(5)：543, articleTitle=Formulation and development of metered dose inhalations of salbutamol in solution form, refAbstract=null), Reference(id=1239218786641965419, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2011, volume=23, issue=11, pageStart=116, pageEnd=null, url=null, language=null, rfNumber=[3], rfOrder=3, authorNames=郑丹红, journalName=海峡药学, refType=null, unstructuredReference=郑丹红. 硫酸沙丁胺醇雾化吸入治疗支气管哮喘急性发作的效果观察及护理[J]. 海峡药学，2011，23(11)：116, articleTitle=硫酸沙丁胺醇雾化吸入治疗支气管哮喘急性发作的效果观察及护理, refAbstract=null), Reference(id=1239218786725851502, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2011, volume=23, issue=11, pageStart=116, pageEnd=null, url=null, language=null, rfNumber=[3], rfOrder=4, authorNames=ZHENG DH, journalName=Strait Pharm J, refType=null, unstructuredReference=ZHENG DH. Observation and nursing of the effect of nebulized inhalation of salbutamol sulfate in the treatment of acute attacks of bronchial asthma[J]. Strait Pharm J，2011，23(11)：116, articleTitle=Observation and nursing of the effect of nebulized inhalation of salbutamol sulfate in the treatment of acute attacks of bronchial asthma, refAbstract=null), Reference(id=1239218786792960368, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2004, volume=null, issue=null, pageStart=495, pageEnd=null, url=null, language=null, rfNumber=[4], rfOrder=5, authorNames=国家食品药品监督管理局药品审评中心, journalName=四川美康医药软件研究开发有限公司. 药物临床信息参考, refType=null, unstructuredReference=国家食品药品监督管理局药品审评中心. 四川美康医药软件研究开发有限公司. 药物临床信息参考[M]. 成都：四川科学技术出版社，2004：495, articleTitle=null, refAbstract=null), Reference(id=1239218786889429363, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2004, volume=null, issue=null, pageStart=495, pageEnd=null, url=null, language=null, rfNumber=[4], rfOrder=6, authorNames=Center for Drug Evaluation，CFDA, journalName=Sichuan Medicom Software Co.，LTD. Clinical Drug Reference, refType=null, unstructuredReference=Center for Drug Evaluation，CFDA. Sichuan Medicom Software Co.，LTD. Clinical Drug Reference[M]. Chengdu：Sichuan Publishing House of Science & Technology，2004：495, articleTitle=null, refAbstract=null), Reference(id=1239218786969121141, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2018, volume=8, issue=12, pageStart=55, pageEnd=null, url=null, language=null, rfNumber=[5], rfOrder=7, authorNames=莫建容, 黄念华, 黎小华, journalName=中国医药科学, refType=null, unstructuredReference=莫建容，黄念华，黎小华. 硫酸沙丁胺醇气雾剂吸入与茶碱控释片治疗急性老年哮喘的临床疗效[J]. 中国医药科学，2018，8(12)：55, articleTitle=硫酸沙丁胺醇气雾剂吸入与茶碱控释片治疗急性老年哮喘的临床疗效, refAbstract=null), Reference(id=1239218787044618616, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2018, volume=8, issue=12, pageStart=55, pageEnd=null, url=null, language=null, rfNumber=[5], rfOrder=8, authorNames=MO JR, HUANG NH, LI XH, journalName=Chin Med Pharm, refType=null, unstructuredReference=MO JR，HUANG NH，LI XH. Clinical efficacy of salbutamol sulfate aerosol inhalation and theophylline controlled release tablets in the treatment of acute senile asthma[J]. Chin Med Pharm，2018，8(12)：55, articleTitle=Clinical efficacy of salbutamol sulfate aerosol inhalation and theophylline controlled release tablets in the treatment of acute senile asthma, refAbstract=null), Reference(id=1239218787115921787, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2017, volume=32, issue=9, pageStart=1683, pageEnd=null, url=null, language=null, rfNumber=[6], rfOrder=9, authorNames=王枫, 兰莉, 乔艳梅, journalName=现代药物与临床, refType=null, unstructuredReference=王枫，兰莉，乔艳梅. 硫酸沙丁胺醇联合氨茶碱治疗小儿哮喘的疗效观察[J]. 现代药物与临床，2017，32(9)：1683, articleTitle=硫酸沙丁胺醇联合氨茶碱治疗小儿哮喘的疗效观察, refAbstract=null), Reference(id=1239218787191419260, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2017, volume=32, issue=9, pageStart=1683, pageEnd=null, url=null, language=null, rfNumber=[6], rfOrder=10, authorNames=WANG F, LAN L, QIAO YM, journalName=Drugs Clin, refType=null, unstructuredReference=WANG F，LAN L，QIAO YM. Clinical observation of salbutamol sulfate combined with aminophylline in treatment of children with asthma[J]. Drugs Clin，2017，32(9)：1683, articleTitle=Clinical observation of salbutamol sulfate combined with aminophylline in treatment of children with asthma, refAbstract=null), Reference(id=1239218787292082558, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2024, volume=39, issue=3, pageStart=680, pageEnd=null, url=null, language=null, rfNumber=[7], rfOrder=11, authorNames=梁利红, 许丽萍, 梁东阁, journalName=现代药物与临床, refType=null, unstructuredReference=梁利红，许丽萍，梁东阁，等. 小儿定喘口服液联合硫酸沙丁胺醇治疗小儿轻中度支气管哮喘的临床研究[J]. 现代药物与临床，2024，39(3)：680, articleTitle=小儿定喘口服液联合硫酸沙丁胺醇治疗小儿轻中度支气管哮喘的临床研究, refAbstract=null), Reference(id=1239218787384357247, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2024, volume=39, issue=3, pageStart=680, pageEnd=null, url=null, language=null, rfNumber=[7], rfOrder=12, authorNames=LIANG LH, XU LP, LIANG DG, journalName=Drug Clin, refType=null, unstructuredReference=LIANG LH，XU LP，LIANG DG，et al. Clinical study on Xiao’er Dingchuan oral liquid combined with salbutamol[J]. Drug Clin，2024，39(3)：680, articleTitle=Clinical study on Xiao’er Dingchuan oral liquid combined with salbutamol, refAbstract=null), Reference(id=1239218787468243329, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2023, volume=54, issue=4, pageStart=540, pageEnd=null, url=null, language=null, rfNumber=[8], rfOrder=13, authorNames=仇中选, 王东, 管丽君, journalName=中国医药工业杂志, refType=null, unstructuredReference=仇中选，王东，管丽君，等. 硫酸沙丁胺醇有关物质的合成[J]. 中国医药工业杂志，2023，54(4)：540, articleTitle=硫酸沙丁胺醇有关物质的合成, refAbstract=null), Reference(id=1239218787552129411, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2023, volume=54, issue=4, pageStart=540, pageEnd=null, url=null, language=null, rfNumber=[8], rfOrder=14, authorNames=QIU ZX, WANG D, GUAN LJ, journalName=Chin J Pharm, refType=null, unstructuredReference=QIU ZX，WANG D，GUAN LJ，et al. Synthesis of the related substances of salbutamol sulfate[J]. Chin J Pharm，2023，54(4)：540, articleTitle=Synthesis of the related substances of salbutamol sulfate, refAbstract=null), Reference(id=1239218787648598404, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[9], rfOrder=15, authorNames=叶小辉, 孙宁云, 戴健, journalName=null, refType=null, unstructuredReference=叶小辉，孙宁云，戴健，等. 一种沙丁胺醇杂质的制备方法及应用：中国，112979480 B[P]. 2023-05-16, articleTitle=一种沙丁胺醇杂质的制备方法及应用：中国, refAbstract=null), Reference(id=1239218787719901575, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[9], rfOrder=16, authorNames=YE XH, SUN NY, DAI J, journalName=null, refType=null, unstructuredReference=YE XH，SUN NY，DAI J，et al. A Preparation Method and Application of Impurities in Salbutamol：China，112979480 B[P]. 2023-05-16, articleTitle=A Preparation Method and Application of Impurities in Salbutamol：China, refAbstract=null), Reference(id=1239218787807981962, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2022, volume=null, issue=null, pageStart=3936, pageEnd=null, url=null, language=null, rfNumber=[10], rfOrder=17, authorNames=null, journalName=null, refType=null, unstructuredReference=EP 11[S]. 2022：3936, articleTitle=null, refAbstract=null), Reference(id=1239218787883479436, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2020, volume=24, issue=2, pageStart=242, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=18, authorNames=王鑫, 刘宏大, 薛雁, journalName=安徽医药, refType=null, unstructuredReference=王鑫，刘宏大，薛雁，等. 高效液相色谱法测定硫酸沙丁胺醇有关物质的含量[J]. 安徽医药，2020，24(2)：242, articleTitle=高效液相色谱法测定硫酸沙丁胺醇有关物质的含量, refAbstract=null), Reference(id=1239218787950588302, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2020, volume=24, issue=2, pageStart=242, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=19, authorNames=WANG X, LIU HD, XUE Y, journalName=Anhui Med Pharm J, refType=null, unstructuredReference=WANG X，LIU HD，XUE Y，et al. HPLC method was used to determine the content of albuterol sulfate[J]. Anhui Med Pharm J，2020，24(2)：242, articleTitle=HPLC method was used to determine the content of albuterol sulfate, refAbstract=null), Reference(id=1239218788013502864, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2012, volume=14, issue=11, pageStart=416, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=20, authorNames=张冬梅, 牛冲, 冷佳蔚, journalName=食品与药品, refType=null, unstructuredReference=张冬梅，牛冲，冷佳蔚. HPLC测定硫酸沙丁胺醇雾化吸入溶液有关物质方法的研究[J]. 食品与药品，2012，14(11)：416, articleTitle=HPLC测定硫酸沙丁胺醇雾化吸入溶液有关物质方法的研究, refAbstract=null), Reference(id=1239218788089000338, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2012, volume=14, issue=11, pageStart=416, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=21, authorNames=ZHANG DM, NIU C, LENG JW, journalName=Food Drug, refType=null, unstructuredReference=ZHANG DM，NIU C，LENG JW. Determination of related substances in salbutamol sulfate nebules inhalation solution by HPLC[J]. Food Drug，2012，14(11)：416, articleTitle=Determination of related substances in salbutamol sulfate nebules inhalation solution by HPLC, refAbstract=null), Reference(id=1239218788172886419, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2002, volume=37, issue=7, pageStart=55, pageEnd=null, url=null, language=null, rfNumber=[13], rfOrder=22, authorNames=左文坚, 史欣, journalName=中国药学杂志, refType=null, unstructuredReference=左文坚，史欣. HPLC测定硫酸沙丁胺醇缓释片有关物质及含量[J]. 中国药学杂志，2002，37(7)：55, articleTitle=HPLC测定硫酸沙丁胺醇缓释片有关物质及含量, refAbstract=null), Reference(id=1239218788235800980, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2002, volume=37, issue=7, pageStart=55, pageEnd=null, url=null, language=null, rfNumber=[13], rfOrder=23, authorNames=ZUO WJ, SHI X, journalName=Chin Pharm J, refType=null, unstructuredReference=ZUO WJ，SHI X. Assay for the content and related substance of salbutamol sulfate sustained release tablets by HPLC[J]. Chin Pharm J，2002，37(7)：55, articleTitle=Assay for the content and related substance of salbutamol sulfate sustained release tablets by HPLC, refAbstract=null), Reference(id=1239218788311298453, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=1583, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=24, authorNames=null, journalName=null, refType=null, unstructuredReference=中华人民共和国药典2020年版. 二部[S]. 2020：1583, articleTitle=null, refAbstract=null), Reference(id=1239218788382601622, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=1583, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=25, authorNames=null, journalName=null, refType=null, unstructuredReference=ChP 2020. Vol Ⅱ[S]. 2020：1583, articleTitle=null, refAbstract=null), Reference(id=1239218788458099095, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=547, pageEnd=null, url=null, language=null, rfNumber=[15], rfOrder=26, authorNames=null, journalName=null, refType=null, unstructuredReference=中华人民共和国药典2020年版. 四部[S]. 2020：547, articleTitle=null, refAbstract=null), Reference(id=1239218788516819352, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=547, pageEnd=null, url=null, language=null, rfNumber=[15], rfOrder=27, authorNames=null, journalName=null, refType=null, unstructuredReference=ChP 2020. Vol Ⅳ[S]. 2020：547, articleTitle=null, refAbstract=null), Reference(id=1239218788604899737, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2013, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=28, authorNames=ICH, journalName=null, refType=null, unstructuredReference=ICH. Harmonised Guideline M7(R2)：Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceutic to Limit Potential Carcinogenic Risk[EB/OL]. Geneva：ICH，2013[2023-04-03]. https://www.ich.org/page/multidisciplinary-guidelines, articleTitle=Harmonised Guideline M7(R2)：Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceutic to Limit Potential Carcinogenic Risk, refAbstract=null), Reference(id=1239218788701368730, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, doi=null, pmid=null, pmcid=null, year=2009, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=29, authorNames=BENIGNI R, BOSSA C, TCHEREMENSKAIA O, journalName=null, refType=null, unstructuredReference=BENIGNI R，BOSSA C，TCHEREMENSKAIA O，et al. Development of Structural Alerts for the In Vivo Micronucleus Assay in Rodents[EB/OL]. Luxembourg：OPOCE，2009[2009-06-03]. https://publications.jrc.ec.europa.eu/repository/handle/JRC52274, articleTitle=Development of Structural Alerts for the In Vivo Micronucleus Assay in Rodents, refAbstract=null)], funds=[Fund(id=1239218786222535008, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, awardId=tscx202306073, language=CN, fundingSource=*泰山产业领军人才工程专项经费(tscx202306073), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1239218776776962053, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=1., ext=[AuthorCompanyExt(id=1239218776785350662, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China), AuthorCompanyExt(id=1239218776793739271, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776776962053, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101)]), AuthorCompany(id=1239218776886013967, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=2., ext=[AuthorCompanyExt(id=1239218776894402574, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776886013967, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.Shandong Jewim Pharmaceutical Co., Ltd., Taian 271000, China), AuthorCompanyExt(id=1239218776898596879, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218776886013967, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. 山东京卫制药有限公司，泰安 271000)]), AuthorCompany(id=1239218777049591825, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, xref=3., ext=[AuthorCompanyExt(id=1239218777066369045, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218777049591825, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.The Fifth People’s Hospital of Jinan, Jinan 250022, China), AuthorCompanyExt(id=1239218777083146263, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, companyId=1239218777049591825, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.济南市第五人民医院，济南 250022)])], figs=[ArticleFig(id=1239218783924056354, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Fig.1, caption=HPLC chromatograms, figureFileSmall=FD0NThxaWgDHaqipmSM8Zw==, figureFileBig=4rLXOLUVjpTEpRrm3bhXcA==, tableContent=null), ArticleFig(id=1239218784016331043, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=图1, caption=典型液相色谱图

1.硫酸沙丁胺醇(salbutamol sulfate)　2.杂质J(impurity J)　3.杂质B(impurity B)　4.杂质A(impurity A)　5.杂质C(impurity C)　6.杂质D(impurity D)　7.杂质H(impurity H)　8.杂质E(impurity E)　9.杂质G(impurity G)　10.杂质N(impurity N)　11.杂质F(impurity F)　12.杂质I(impurity I)

, figureFileSmall=FD0NThxaWgDHaqipmSM8Zw==, figureFileBig=4rLXOLUVjpTEpRrm3bhXcA==, tableContent=null), ArticleFig(id=1239218784188297514, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Fig.2, caption=Chromatograms of API after forced degradation, figureFileSmall=qnmGNBRA8IaVDiczFMdoeQ==, figureFileBig=/Wo4dPvY31u6NJFcyhHqww==, tableContent=null), ArticleFig(id=1239218784267989292, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=图2, caption=API强制降解试验色谱图, figureFileSmall=qnmGNBRA8IaVDiczFMdoeQ==, figureFileBig=/Wo4dPvY31u6NJFcyhHqww==, tableContent=null), ArticleFig(id=1239218784381235503, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Fig.3, caption=Scatter diagram of the results of impurity content, figureFileSmall=tpoTwLqvh4nMu2dRj/IUeQ==, figureFileBig=wKVgwaSzXQyZn5tpDlFZJA==, tableContent=null), ArticleFig(id=1239218784490287413, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=图3, caption=各杂质测定结果柱状散点图, figureFileSmall=tpoTwLqvh4nMu2dRj/IUeQ==, figureFileBig=wKVgwaSzXQyZn5tpDlFZJA==, tableContent=null), ArticleFig(id=1239218784607727928, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Tab.1, caption=

Gradient elution

, figureFileSmall=null, figureFileBig=null, tableContent=
t/min流动相比例（ratio of mobile phase）/%
AB
08020
308020
406040
506040
50.18020
608020
), ArticleFig(id=1239218784771305788, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=表1, caption=

梯度洗脱

, figureFileSmall=null, figureFileBig=null, tableContent=
t/min流动相比例（ratio of mobile phase）/%
AB
08020
308020
406040
506040
50.18020
608020
), ArticleFig(id=1239218784871969085, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Tab.2, caption=

Regression equation，r，LOQ and LOD

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		回归方程
(regression equation)		 r相对校正因子
(relative correction factor)		LOQ/(μg·mL-1)LOD/(μg·mL-1)
硫酸沙丁胺醇(salbutamol sulfate) Y=0.628 4C+0.003 20.999 9/0.0500.017
杂质A(impurity A) Y=0.506 1C+0.002 70.999 91.240.1000.033
杂质B(impurity B) Y=0.640 1C+0.001 30.999 90.980.0500.017
杂质C(impurity C) Y=0.592 6C+0.002 80.999 91.060.1000.033
杂质D(impurity D) Y=1.948 4C+0.003 40.999 90.320.0500.017
杂质E(impurity E) Y=0.531 4C-0.004 60.999 91.180.2000.067
杂质F(impurity F) Y=0.654 6C+0.001 50.999 90.960.0500.017
杂质G(impurity G) Y=0.265 3C-0.002 10.999 92.370.1500.050
杂质H(impurity H) Y=0.494 0C+0.006 40.999 91.270.2000.067
杂质I(impurity I) Y=0.766 6C+0.000 71.0000.820.0250.083
杂质J(impurity J) Y=0.738 1C+0.004 10.999 90.850.0500.017
杂质N(impurity N) Y=0.774 3C+0.002 60.999 90.810.0500.017
), ArticleFig(id=1239218784981020993, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=表2, caption=

回归方程、相关系数、定量限和检测限

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		回归方程
(regression equation)		 r相对校正因子
(relative correction factor)		LOQ/(μg·mL-1)LOD/(μg·mL-1)
硫酸沙丁胺醇(salbutamol sulfate) Y=0.628 4C+0.003 20.999 9/0.0500.017
杂质A(impurity A) Y=0.506 1C+0.002 70.999 91.240.1000.033
杂质B(impurity B) Y=0.640 1C+0.001 30.999 90.980.0500.017
杂质C(impurity C) Y=0.592 6C+0.002 80.999 91.060.1000.033
杂质D(impurity D) Y=1.948 4C+0.003 40.999 90.320.0500.017
杂质E(impurity E) Y=0.531 4C-0.004 60.999 91.180.2000.067
杂质F(impurity F) Y=0.654 6C+0.001 50.999 90.960.0500.017
杂质G(impurity G) Y=0.265 3C-0.002 10.999 92.370.1500.050
杂质H(impurity H) Y=0.494 0C+0.006 40.999 91.270.2000.067
杂质I(impurity I) Y=0.766 6C+0.000 71.0000.820.0250.083
杂质J(impurity J) Y=0.738 1C+0.004 10.999 90.850.0500.017
杂质N(impurity N) Y=0.774 3C+0.002 60.999 90.810.0500.017
), ArticleFig(id=1239218785081684292, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Tab.3, caption=

Results of recovery test

, figureFileSmall=null, figureFileBig=null, tableContent=
类别
(item)		杂质
(impurity)		加入量
(added)/μg		测得量
(measured)/μg		回收率
(recovery) /%		平均回收率
(average recovery，n=9)/%		RSD(n=9)/%
原料药(API)杂质A(impurity A)15.28316.098105.3102.83.8
19.10319.693103.1
22.92422.931100.0
杂质B(impurity B)15.80816.684105.5104.81.5
19.76020.695104.7
23.71224.681104.1
杂质C(impurity C)16.42517.330105.5102.32.6
20.53220.664100.6
24.63824.824100.8
杂质D(impurity D)13.29114.020105.5102.92.1
16.61316.863101.5
19.93620.263101.6
杂质E(impurity E)16.15315.75097.596.72.2
20.19219.61897.2
24.23023.14295.5
杂质F(impurity F)10.72911.166104.1103.63.0
13.41113.629101.6
16.09316.925105.2
杂质G(impurity G)20.67120.688100.1100.23.5
25.83925.12697.2
31.00632.002103.2
杂质H(Impurity H)15.90516.535104.099.73.7
19.88119.23696.8
23.85823.45298.3
杂质I(impurity I)15.51515.792101.8101.11.1
19.39419.507100.6
23.27323.504101.0
杂质J(impurity J)14.28813.49794.595.21.4
17.86017.20996.4
21.43220.28094.6
杂质N(impurity N)13.67513.826101.1101.60.80
17.09317.458102.1
20.51220.836101.6
制剂(preparation)杂质A(impurity A)15.28315.547101.7100.41.8
19.10319.142100.2
22.92422.73799.2
杂质B(Impurity B)15.80815.943100.9100.11.5
19.76019.72499.8
23.71223.58299.5
杂质C(impurity C)16.42516.614101.2100.81.6
20.53220.719100.9
24.63824.687100.2
杂质D(impurity D)13.29113.480101.4100.21.2
16.61316.56199.7
19.93619.82799.5
杂质E(impurity E)16.15316.405101.6102.82.9
20.19221.115104.6
24.23024.795102.3
杂质F(impurity F)10.72910.972102.3101.81.2
13.41113.575101.2
16.09316.407102.0
杂质G(impurity G)20.67121.313103.1101.52.8
25.83926.064100.9
31.00631.189100.6
杂质H(impurity H)15.90515.84399.698.72.0
19.88119.43397.8
23.85823.51898.6
杂质I(impurity I)15.51515.46799.7100.41.4
19.39419.37799.9
23.27323.612101.5
杂质J(impurity J)14.28814.758103.3102.01.4
17.86018.217102.0
21.43221.609100.8
杂质N(impurity N)13.67513.873101.5101.81.5
17.09317.269101.0
20.51221.091102.8
), ArticleFig(id=1239218785203319110, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=表3, caption=

回收率试验结果

, figureFileSmall=null, figureFileBig=null, tableContent=
类别
(item)		杂质
(impurity)		加入量
(added)/μg		测得量
(measured)/μg		回收率
(recovery) /%		平均回收率
(average recovery，n=9)/%		RSD(n=9)/%
原料药(API)杂质A(impurity A)15.28316.098105.3102.83.8
19.10319.693103.1
22.92422.931100.0
杂质B(impurity B)15.80816.684105.5104.81.5
19.76020.695104.7
23.71224.681104.1
杂质C(impurity C)16.42517.330105.5102.32.6
20.53220.664100.6
24.63824.824100.8
杂质D(impurity D)13.29114.020105.5102.92.1
16.61316.863101.5
19.93620.263101.6
杂质E(impurity E)16.15315.75097.596.72.2
20.19219.61897.2
24.23023.14295.5
杂质F(impurity F)10.72911.166104.1103.63.0
13.41113.629101.6
16.09316.925105.2
杂质G(impurity G)20.67120.688100.1100.23.5
25.83925.12697.2
31.00632.002103.2
杂质H(Impurity H)15.90516.535104.099.73.7
19.88119.23696.8
23.85823.45298.3
杂质I(impurity I)15.51515.792101.8101.11.1
19.39419.507100.6
23.27323.504101.0
杂质J(impurity J)14.28813.49794.595.21.4
17.86017.20996.4
21.43220.28094.6
杂质N(impurity N)13.67513.826101.1101.60.80
17.09317.458102.1
20.51220.836101.6
制剂(preparation)杂质A(impurity A)15.28315.547101.7100.41.8
19.10319.142100.2
22.92422.73799.2
杂质B(Impurity B)15.80815.943100.9100.11.5
19.76019.72499.8
23.71223.58299.5
杂质C(impurity C)16.42516.614101.2100.81.6
20.53220.719100.9
24.63824.687100.2
杂质D(impurity D)13.29113.480101.4100.21.2
16.61316.56199.7
19.93619.82799.5
杂质E(impurity E)16.15316.405101.6102.82.9
20.19221.115104.6
24.23024.795102.3
杂质F(impurity F)10.72910.972102.3101.81.2
13.41113.575101.2
16.09316.407102.0
杂质G(impurity G)20.67121.313103.1101.52.8
25.83926.064100.9
31.00631.189100.6
杂质H(impurity H)15.90515.84399.698.72.0
19.88119.43397.8
23.85823.51898.6
杂质I(impurity I)15.51515.46799.7100.41.4
19.39419.37799.9
23.27323.612101.5
杂质J(impurity J)14.28814.758103.3102.01.4
17.86018.217102.0
21.43221.609100.8
杂质N(impurity N)13.67513.873101.5101.81.5
17.09317.269101.0
20.51221.091102.8
), ArticleFig(id=1239218785295593801, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Tab.4, caption=

Robustness test results

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		梯度1保留时间/分离度
(gradient 1 retention time/peak resolution)		梯度2保留时间/分离度
(gradient 2 retention time/peak resolution)		保留时间/分离度
(retention time/peak resolution)
硫酸沙丁胺醇(salbutamol sulfate)6.58/-6.542/-6.722/-
杂质J(impurityJ)7.295/3.157.248/3.157.443/3.07
杂质B(impurityB)9.300/7.539.233/7.459.499/7.55
杂质A(impurityA)9.903/1.969.833/1.9510.136/2.04
杂质C(impurityC)14.957/12.5814.852/12.4815.354/13.05
杂质D(impurityD)19.278/7.5219.15/7.4719.799/8.08
杂质H(impurityH)23.738/6.2023.598/6.0424.385/6.71
杂质E(impurityE)28.465/5.4228.313/5.3129.292/5.90
杂质G(impurityG)35.958/12.2037.330/11.7837.419/12.64
杂质N(impurityN)38.307/4.3239.368/4.8338.703/4.62
杂质F(impurityF)39.185/5.0440.653/5.3139.559/5.02
杂质I(impurityI)43.250/25.7845.313/26.9743.640/25.87
), ArticleFig(id=1239218785404645708, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=表4, caption=

耐用性试验结果

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		梯度1保留时间/分离度
(gradient 1 retention time/peak resolution)		梯度2保留时间/分离度
(gradient 2 retention time/peak resolution)		保留时间/分离度
(retention time/peak resolution)
硫酸沙丁胺醇(salbutamol sulfate)6.58/-6.542/-6.722/-
杂质J(impurityJ)7.295/3.157.248/3.157.443/3.07
杂质B(impurityB)9.300/7.539.233/7.459.499/7.55
杂质A(impurityA)9.903/1.969.833/1.9510.136/2.04
杂质C(impurityC)14.957/12.5814.852/12.4815.354/13.05
杂质D(impurityD)19.278/7.5219.15/7.4719.799/8.08
杂质H(impurityH)23.738/6.2023.598/6.0424.385/6.71
杂质E(impurityE)28.465/5.4228.313/5.3129.292/5.90
杂质G(impurityG)35.958/12.2037.330/11.7837.419/12.64
杂质N(impurityN)38.307/4.3239.368/4.8338.703/4.62
杂质F(impurityF)39.185/5.0440.653/5.3139.559/5.02
杂质I(impurityI)43.250/25.7845.313/26.9743.640/25.87
), ArticleFig(id=1239218785509503312, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Tab.5, caption=

Results of related substances in salbutamol sulfate inhalation aerosol

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		含量（content）/%
a企业检出批次
(Co. a detection batch)		b企业检出批次
(Co. b detection batch)		c企业检出批次
(Co. c detection batch)		d企业检出批次
(Co.d detection batch)
杂质A(impurity A)0.009~0.032（39）0.009~0.036（8）0.009（1）0.015（1）
杂质B(impurity B)-*0.002~0.009（20）--
杂质C(impurity C)0.032~0.071（39）0.005~0.062（11）0.035~0.047（5）0.008~0.047（29）
杂质D(impurity D)0.008~0.019（39）0.009~0.050（32）0.015~0.022（5）0.007~0.020（34）
杂质F(impurity F)0.071~0.159（39）0.009~0.073（32）0.086~0.121（5）0.037~0.075（34）
杂质I(impurity I)0.006（1）0.003~0.010（9）-0.006~0.020（33）
杂质J(impurity J)-0.006（1）--
杂质N(impurity N)0.034~0.075（39）0.002~0.058（30）0.006~0.010（5）0.004~0.057（32）
未知杂质（unknown impurity）RRT 0.480.014~0.021（2）--0.011~0.056（10）
RRT 0.54--0.013~0.016（3）0.016~0.093（34）
RRT 0.59--0.033~0.083（5）0.004~0.093（34）
RRT 0.70-0.004~0.014（9）0.009（1）0.010~0.030（24）
RRT 0.880.011~0.026（39）--0.009~0.031（7）
RRT 1.32-0.008~0.046（9）0.041~0.053（5）0.007~0.041（18）
RRT 1.900.006~0.009（8）0.006~0.102（11）0.094~0.117（5）0.009~0.038（6）
RRT 2.42---0.008~0.017（22）
RRT 3.280.041~0.082（39）0.006~0.180（32）0.067~0.124（5）0.087~0.214（34）
RRT 5.76---0.007~0.044（18）
RRT 5.840.008~0.022（39）0.010~0.081（5）0.134（1）0.016~0.089（5）
RRT 6.040.005~0.009（8）0.003~0.010（16）-0.011~0.154（4）
最大未知单杂(unspecified impurity)0.041~0.082（39）0.006~0.180（32）0.094~0.124（5）0.090~0.214（34）
各杂质总和(total impurities)0.233~0.452（39）0.053~0.494（32）0.393~0.600（5）0.303~0.630（34）
), ArticleFig(id=1239218785622749524, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=表5, caption=

硫酸沙丁胺醇吸入气雾剂有关物质测定结果

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		含量（content）/%
a企业检出批次
(Co. a detection batch)		b企业检出批次
(Co. b detection batch)		c企业检出批次
(Co. c detection batch)		d企业检出批次
(Co.d detection batch)
杂质A(impurity A)0.009~0.032（39）0.009~0.036（8）0.009（1）0.015（1）
杂质B(impurity B)-*0.002~0.009（20）--
杂质C(impurity C)0.032~0.071（39）0.005~0.062（11）0.035~0.047（5）0.008~0.047（29）
杂质D(impurity D)0.008~0.019（39）0.009~0.050（32）0.015~0.022（5）0.007~0.020（34）
杂质F(impurity F)0.071~0.159（39）0.009~0.073（32）0.086~0.121（5）0.037~0.075（34）
杂质I(impurity I)0.006（1）0.003~0.010（9）-0.006~0.020（33）
杂质J(impurity J)-0.006（1）--
杂质N(impurity N)0.034~0.075（39）0.002~0.058（30）0.006~0.010（5）0.004~0.057（32）
未知杂质（unknown impurity）RRT 0.480.014~0.021（2）--0.011~0.056（10）
RRT 0.54--0.013~0.016（3）0.016~0.093（34）
RRT 0.59--0.033~0.083（5）0.004~0.093（34）
RRT 0.70-0.004~0.014（9）0.009（1）0.010~0.030（24）
RRT 0.880.011~0.026（39）--0.009~0.031（7）
RRT 1.32-0.008~0.046（9）0.041~0.053（5）0.007~0.041（18）
RRT 1.900.006~0.009（8）0.006~0.102（11）0.094~0.117（5）0.009~0.038（6）
RRT 2.42---0.008~0.017（22）
RRT 3.280.041~0.082（39）0.006~0.180（32）0.067~0.124（5）0.087~0.214（34）
RRT 5.76---0.007~0.044（18）
RRT 5.840.008~0.022（39）0.010~0.081（5）0.134（1）0.016~0.089（5）
RRT 6.040.005~0.009（8）0.003~0.010（16）-0.011~0.154（4）
最大未知单杂(unspecified impurity)0.041~0.082（39）0.006~0.180（32）0.094~0.124（5）0.090~0.214（34）
各杂质总和(total impurities)0.233~0.452（39）0.053~0.494（32）0.393~0.600（5）0.303~0.630（34）
), ArticleFig(id=1239218785706635607, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Tab.6, caption=

Impurity detection results and possible pathways

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		检出率
(detectable rate)/%		检出量
(checkout content)/%		可能产生的途径
(possible pathway)
杂质A(impurity A)44.50.009~0.036工艺杂质(process impurity)
杂质B(impurity B)18.20.002~0.009工艺杂质(process impurity)
杂质C(impurity C)76.40.005~0.071工艺杂质(process impurity)
杂质D(impurity D)100.00.007~0.050酸、碱、氧化、热、光照降解杂质(hydrolytic by acid or base，oxidative，heat，photolytic impurity)
杂质E(impurity E)--工艺杂质(process impurity)
杂质F(impurity F)100.00.009~0.159酸、光照、热降解杂质(hydrolytic by acid，photolytic，heat impurity)
杂质G(impurity G)--工艺杂质(process impurity)
杂质H(impurity H)--工艺杂质(process impurity)
杂质I(impurity I)39.10.003~0.020中间体、碱降解杂质(Intermediate，hydrolytic by base impurity)
杂质J(impurity J)0.90.006氧化降解杂质(oxidative impurity)
杂质N(impurity N)96.40.002~0.075酸、碱、光照降解杂质(hydrolytic by acid or base，photolytic impurity)
), ArticleFig(id=1239218785807298906, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=表6, caption=

杂质检出情况及可能产生的途径

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)		检出率
(detectable rate)/%		检出量
(checkout content)/%		可能产生的途径
(possible pathway)
杂质A(impurity A)44.50.009~0.036工艺杂质(process impurity)
杂质B(impurity B)18.20.002~0.009工艺杂质(process impurity)
杂质C(impurity C)76.40.005~0.071工艺杂质(process impurity)
杂质D(impurity D)100.00.007~0.050酸、碱、氧化、热、光照降解杂质(hydrolytic by acid or base，oxidative，heat，photolytic impurity)
杂质E(impurity E)--工艺杂质(process impurity)
杂质F(impurity F)100.00.009~0.159酸、光照、热降解杂质(hydrolytic by acid，photolytic，heat impurity)
杂质G(impurity G)--工艺杂质(process impurity)
杂质H(impurity H)--工艺杂质(process impurity)
杂质I(impurity I)39.10.003~0.020中间体、碱降解杂质(Intermediate，hydrolytic by base impurity)
杂质J(impurity J)0.90.006氧化降解杂质(oxidative impurity)
杂质N(impurity N)96.40.002~0.075酸、碱、光照降解杂质(hydrolytic by acid or base，photolytic impurity)
), ArticleFig(id=1239218785895379293, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=EN, label=Tab.7, caption=

QSAR genotoxicity evaluation results

, figureFileSmall=null, figureFileBig=null, tableContent=
成分(component)ICH M7分类
(ICH M7 class)		Derek预测
(Derek prediction)		Sarah预测
(Sarah prediction)		警示结构
(structural alert)
杂质A(impurity A)5无(No)
杂质B(impurity B)5无(No)
杂质C(impurity C)5无(No)
杂质D(impurity D)2烷基醛(aldehyde)
杂质E(impurity E)5无(No)
杂质F(impurity F)5无(No)
杂质G(impurity G)5无(No)
杂质H(impurity H)5无(No)
杂质I(impurity I)5无(No)
杂质J(impurity J)5无(No)
杂质N(impurity N)5无(No)
), ArticleFig(id=1239218786029597024, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1239184760455623313, language=CN, label=表7, caption=

QSAR基因毒性评价结果

, figureFileSmall=null, figureFileBig=null, tableContent=
成分(component)ICH M7分类
(ICH M7 class)		Derek预测
(Derek prediction)		Sarah预测
(Sarah prediction)		警示结构
(structural alert)
杂质A(impurity A)5无(No)
杂质B(impurity B)5无(No)
杂质C(impurity C)5无(No)
杂质D(impurity D)2烷基醛(aldehyde)
杂质E(impurity E)5无(No)
杂质F(impurity F)5无(No)
杂质G(impurity G)5无(No)
杂质H(impurity H)5无(No)
杂质I(impurity I)5无(No)
杂质J(impurity J)5无(No)
杂质N(impurity N)5无(No)
)], attaches=null, journal=Journal(id=1205114436974182403, delFlag=0, nameCn=药物分析杂志, nameEn=Chinese Journal of Pharmaceutical Analysis, nameHistory1=null, nameHistory2=null, issn=0254-1793, eissn=, cn=11-2224/R, coden=null, periodic=月刊, language=CN, oaType=1, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=, officePhone=, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=E+iq5BU+frOtpo6YF6JpQQ==, journalPrice=null, startedYear=null, abbrevIsoEn=Chinese Journal of Pharmaceutical Analysis, journalRemark=null, publicationField=null, createdTime=1765251271721, updatedTime=1765252167692, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=C, firstLetterEn=C, subjectCode=Life Sciences, subjectName=生命医学, subjectCodeEn=Life Sciences, subjectNameEn=null, picCn=E+iq5BU+frOtpo6YF6JpQQ==, picEn=n/3T/+AptjYTGmmMsE/a0Q==, jcr=null, cjcr=null, exts=[JournalExt(id=1205118195070906572, language=CN, name=药物分析杂志, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1765252167718, updatedTime=1765252167718, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ywfxauthor.manuscriptcloud.com/login, submissionEditorUrl=https://ywfxeditor.manuscriptcloud.com/login, submissionReviewUrl=https://ywfxauthor.manuscriptcloud.com/login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1205118195133821133, language=EN, name=Chinese Journal of Pharmaceutical Analysis, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1765252167733, updatedTime=1765252167733, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ywfxauthor.manuscriptcloud.com/login, submissionEditorUrl=https://ywfxeditor.manuscriptcloud.com/login, submissionReviewUrl=https://ywfxauthor.manuscriptcloud.com/login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1205117023404326918, websiteList=[Website(id=1205118568045195478, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1205117023404326918, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ywfxzz/CN, language=CN, createTime=1765252256642, createBy=18614031015, updateTime=1765252521924, updateBy=18614031015, name=药物分析杂志-中文, tplId=1146099689490845704, title=药物分析杂志, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1205154326156128935, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=articleTextType, value=kx, createTime=1765260782040, updateTime=1765260782040, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326135157412, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=banner, value=null, createTime=1765260782035, updateTime=1765260782035, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326172906154, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=grayFlag, value=0, createTime=1765260782044, updateTime=1765260782044, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326126768803, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=logo, value=https://castjournals.cast.org.cn/joweb/ywfxzz/CN/file/pic?fileId=5+7UKv7ckvsJ8AsWJeRI6g==, createTime=1765260782033, updateTime=1765260782033, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326181294764, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=minRunFlag, value=0, createTime=1765260782046, updateTime=1765260782046, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326147740326, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ywfxzz/CN/file/pic, createTime=1765260782038, updateTime=1765260782038, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326177100459, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=silenceFlag, value=0, createTime=1765260782045, updateTime=1765260782045, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326143546021, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1765260782037, updateTime=1765260782037, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326160323240, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=themeColor, value=null, createTime=1765260782041, updateTime=1765260782041, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154326164517545, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568045195478, code=themeStyle, value=null, createTime=1765260782042, updateTime=1765260782042, creator=18614031015, updator=18614031015)]), Website(id=1205118568124887259, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1205117023404326918, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ywfxzz/EN, language=EN, createTime=1765252256661, createBy=18614031015, updateTime=1765252537379, updateBy=18614031015, name=药物分析杂志-英文, tplId=1146101810881728533, title=Chinese Journal of Pharmaceutical Analysis, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1205154361170174338, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=articleTextType, value=kx, createTime=1765260790388, updateTime=1765260790388, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361145008511, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=banner, value=null, createTime=1765260790382, updateTime=1765260790382, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361195340165, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=grayFlag, value=0, createTime=1765260790394, updateTime=1765260790394, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361132425598, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=logo, value=https://castjournals.cast.org.cn/joweb/ywfxzz/EN/file/pic?fileId=5+7UKv7ckvsJ8AsWJeRI6g==, createTime=1765260790379, updateTime=1765260790379, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361207923079, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=minRunFlag, value=0, createTime=1765260790397, updateTime=1765260790397, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361157591425, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ywfxzz/EN/file/pic, createTime=1765260790385, updateTime=1765260790385, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361199534470, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=silenceFlag, value=0, createTime=1765260790396, updateTime=1765260790396, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361149202816, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1765260790383, updateTime=1765260790383, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361174368643, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=themeColor, value=null, createTime=1765260790389, updateTime=1765260790389, creator=18614031015, updator=18614031015), WebsiteProps(id=1205154361186951556, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1205118568124887259, code=themeStyle, value=null, createTime=1765260790392, updateTime=1765260790392, creator=18614031015, updator=18614031015)])], journalTitle=药物分析杂志, weixinUrl=null, journalUrl=null, iacademicId=null, status=1, seqNo=null, journalTitleEn=Chinese Journal of Pharmaceutical Analysis, journalPhotoCn=E+iq5BU+frOtpo6YF6JpQQ==, journalPhotoEn=n/3T/+AptjYTGmmMsE/a0Q==, journalFirstLetter=C, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false), detailUrlCn=https://castjournals.cast.org.cn/joweb/ywfxzz/CN/10.16155/j.0254-1793.2024-0227, detailUrlEn=https://castjournals.cast.org.cn/joweb/ywfxzz/EN/10.16155/j.0254-1793.2024-0227, pdfUrlCn=https://castjournals.cast.org.cn/joweb/ywfxzz/CN/PDF/10.16155/j.0254-1793.2024-0227, pdfUrlEn=https://castjournals.cast.org.cn/joweb/ywfxzz/EN/PDF/10.16155/j.0254-1793.2024-0227, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, reference=null)
收藏切换
国家药品抽检中硫酸沙丁胺醇吸入气雾剂有关物质研究*
收藏切换
PDF下载
张连义 1 , 李文馨 1 , 李铁军 2 , 牛冲 1 , 杨书娟 1 , 王文心 1 , 窦艳丽 1 , 郑静 1 , 潘相蜜 3, ** , 徐玉文 1, 2, **
药物分析杂志 | 安全监测 2024,44(12): 2078-2087
收起
收藏切换
药物分析杂志 | 安全监测 2024, 44(12): 2078-2087
国家药品抽检中硫酸沙丁胺醇吸入气雾剂有关物质研究*
全屏
张连义1 , 李文馨1, 李铁军2, 牛冲1, 杨书娟1, 王文心1, 窦艳丽1, 郑静1, 潘相蜜3, ** , 徐玉文1, 2, **
作者信息
  • 1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101
  • 2. 山东京卫制药有限公司，泰安 271000
  • 3.济南市第五人民医院，济南 250022

    • Tel：18853105319；E-mail：

通讯作者:

**潘相蜜　Tel：18668991066；E-mail：
徐玉文　Tel：13553158409；E-mail：
Research on related substances of salbutamol sulfate inhalation aerosol in national drug sampling and testing*
Lian-yi ZHANG1 , Wen-xin LI1, Tie-jun LI2, Chong NIU1, Shu-juan YANG1, Wen-xin WANG1, Yan-li DOU1, Jing ZHENG1, Xiang-mi PAN3, ** , Yu-wen XU1, 2, **
Affiliations
  • 1.Shandong Institute for Food and Drug Control, NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs, Industrial Technology Foundation Public Service Platform, Jinan 250101, China
  • 2.Shandong Jewim Pharmaceutical Co., Ltd., Taian 271000, China
  • 3.The Fifth People’s Hospital of Jinan, Jinan 250022, China
出版时间: 2024-12-31 doi: 10.16155/j.0254-1793.2024-0227
文章导航
收藏切换
摘要
收起
目的：

对国家药品抽检品种硫酸沙丁胺醇吸入气雾剂的有关物质进行探索性研究，比较各企业样品之间含有杂质的情况，以评价药品质量。

方法：

采用HPLC外标法同时测定硫酸沙丁胺醇吸入气雾剂中有关物质A、B、C、D、E、F、G、H、I、J、N及其他未知杂质含量。采用Thermo Syncronis C8（250 mm×4.6 mm，5 μm）色谱柱；以庚烷磺酸钠溶液-乙腈为流动相，进行线性梯度洗脱；流速1.0 mL·min-1；柱温40 ℃；检测波长220 nm；进样体积20 μL。结合强制降解试验探讨杂质来源，并采用毒性预测软件进行杂质毒性评估。

结果：

经方法验证，方法专属性良好，各杂质峰之间分离度均>1.5；精密度试验的RSD为0.30%~1.7%（n=6）；线性范围在0.050~5.000 μg·mL-1（r=0.999 9）；定量限在0.025~0.200 μg·mL-1，检测限在0.008~0.070 μg·mL-1；原料药重复性的RSD为0.80%~3.8%，平均回收率95.2%~104.8%；吸入气雾剂重复性的RSD为1.2%~2.9%，回收率98.7%~102.8%。强制降解试验表明，杂质D、F、I、J、N均为降解杂质。对抽检的110批次样品进行检测，有关物质结果均符合规定。各企业样品中，杂质C、D、F、N检出频次较高，杂质E、G、H均未检出，杂质J仅检出1批次。其中杂质D的QSAR软件预测ICH M7（R2）分类为2级。

结论：

建立的方法灵敏准确，可准确地对硫酸沙丁胺醇气雾剂的有关物质含量进行定量测定，能为科学监管提供有效的技术支持。应对杂质D进行进一步的毒性研究，并确定合理的限度。

国家药品抽检  /  探索性研究  /  硫酸沙丁胺醇吸入气雾剂  /  有关物质  /  杂质来源  /  破坏试验  /  相对校正因子  /  高效液相色谱法  /  定量构效关系
Objective:

To study the related substances in salbutamol sulfate inhalation aerosol during national drug sampling and testing, and to compare the impurity content and evaluate the quality between samples from various enterprises.

Methods:

HPLC external standard method was utilized to simultaneously determine the content of related substances A, B, C, D, E, F, G, H, I, J, N, and other unknown impurities in salbutamol sulfate inhalation aerosol. Thermo Synchronis C8 chromatography column (250 mm×4.6 mm, 5 μm) was used. Sodium heptane sulfonate solution-acetonitrile was used as the mobile phase. Linear gradient elution was performed and the flow rate was 1.0 mL·min-1. Column temperature was 40 ℃ and detection wavelength was 220 nm. Injection volume was 20 μL. The sources of impurities through forced degradation experiments were explored. Toxicity prediction software for impurity toxicity assessment was applied.

Results:

After method validation, the specificity of the method was good, and the separation degree between each impurity peak was greater than 1.5. RSDs of precision test were 0.30%-1.7%(n=6)；mass concentrations of linear range were from 0.050 to 5.000 μg·mL-1(r=0.999 9). Limit of quantitative was in the range of 0.025-0.200 μg·mL-1, limit of detection was in the range of 0.008-0.070 μg·mL-1. The repeatability RSD of raw materials was 0.80%-3.8%, and the recovery rate was 95.2%-104.8%. The repeatability RSD of inhaled aerosol was 1.2%-2.9%, and the recovery rate was 98.7%-102.8%. The forced degradation test showed that impurities D, F, I, J, and N were all degradation impurities. 110 batches of samples were checked and the results of the relevant substances met the regulations. In the samples of diverse enterprises, impurities C, D, F, and N were detected more frequently, while impurities E, G, and H were not detected. Impurity J was only detected in one batch. The predicted impurity D by QSAR software falls to ICH M7 (R2) level 2.

Conclusion:

The established method is sensitive and accurate, and can accurately quantify the content of related substances in salbutamol sulfate aerosol, providing effective technical support for systematic supervision. Further toxicity studies should be conducted on impurity D and reasonable limits should be established.

national drug sampling  /  exploratory research  /  salbutamol sulfate inhalation aerosol  /  related substances  /  source of impurities  /  forced degradation test  /  relative correction factor  /  high performance liquid chromatography  /  quantitative structure-activity relationship
张连义, 李文馨, 李铁军, 牛冲, 杨书娟, 王文心, 窦艳丽, 郑静, 潘相蜜, 徐玉文. 国家药品抽检中硫酸沙丁胺醇吸入气雾剂有关物质研究*. 药物分析杂志, 2024 , 44 (12) : 2078 -2087 . DOI: 10.16155/j.0254-1793.2024-0227
Lian-yi ZHANG, Wen-xin LI, Tie-jun LI, Chong NIU, Shu-juan YANG, Wen-xin WANG, Yan-li DOU, Jing ZHENG, Xiang-mi PAN, Yu-wen XU. Research on related substances of salbutamol sulfate inhalation aerosol in national drug sampling and testing*[J]. Chinese Journal of Pharmaceutical Analysis, 2024 , 44 (12) : 2078 -2087 . DOI: 10.16155/j.0254-1793.2024-0227
正文
收起
硫酸沙丁胺醇化学名为4-羟基-α’-[(叔丁氨基)甲基]-1，3-苯二甲醇硫酸盐，是一种高选择性的β2肾上腺素受体激动药，它能选择性的激动气管平滑肌表面的β2受体，起到舒张支气管，促进纤毛运动的作用。临床上常用剂型为雾化吸入溶液剂、片剂、胶囊剂、注射剂等，用于治疗哮喘或慢阻肺（chronic obstructive pulmoriary disease，COPD）、肺部感染等疾病。吸入气雾剂具有起效快，疗效好，同时减少不良反应等优点，已成为一种倍受关注的给药方式[1-4]，也可用于联合给药[5-7]。经查询国家药监局网站数据库，国内硫酸沙丁胺醇吸入气雾剂有3家企业生产，进口原研产品为Glaxo Wellcome，S.A.生产，规格为每罐200揿，每揿0.1 mg。
硫酸沙丁胺醇原料中含有多种杂质[8-10]。2020年版《中华人民共和国药典》（简称《中国药典》）二部采用等度洗脱方法测定硫酸沙丁胺醇中有关物质，仅对单个杂质和杂质总量进行控制，未对工艺杂质或降解杂质进行针对性的控制，并且分析时间长，效率较低。EP 11.0收载硫酸沙丁胺醇原料，采用超高效液相色谱法测定有关物质，流动相中需加入三乙胺改善峰型。有文献报道了硫酸沙丁胺醇有关物质检测方法[11-13]，有一定借鉴意义，但未能给出各杂质的相对校正因子。
为快速准确的测定样品中的杂质，本文参考2020年版《中国药典》和EP 11.0中硫酸沙丁胺醇有关物质检测方法，对杂质A、B、C、D、E、F、G、H、I、J、N等11个杂质进行检测，并对方法进行优化。按照2020年版《中国药典》四部通则9101分析方法验证指导原则进行方法学验证，可同时用于检测硫酸沙丁胺醇原料及吸入气雾剂中的有关物质。本文结合国家药品抽检计划，考察了国内各企业产品的有关物质情况，与原研制剂的杂质谱进行比较，探讨杂质来源，从而有助于全面评价该品种药品质量。
1　仪器与试药
收起
1.1　仪器
UltiMate 3000型高效液相色谱仪（Thermo Fisher Scientific公司），Agilent 1260高效液相色谱仪（Agilent公司），CP225D型十万分之一电子天平（Sartorius公司），pH计（Mettler-Toledo Group公司）
1.2　试药
硫酸沙丁胺醇对照品（硫酸盐，批号100328-201804，含量99.4%）、杂质J对照品（盐酸盐，批号101409-201601，含量100%）购于中国食品药品检定研究院；杂质A（批号1022-RB-0003，含量95.9%）、杂质C（批号1227-RB-0010，含量98.9%）、杂质E（批号1019-RB-0021，含量98.4%）、杂质H（批号1020-RB-0025，含量95.4%）、杂质N（双甲酸盐，批号1227-RB-0011，含量100%），均购于广州佳途科技股份有限公司；杂质B（批号6.0，含量100%）、杂质D（硫酸盐，批号7.0，含量100%）、杂质F（硫酸盐，批号9.0，含量80.1%）、杂质G（盐酸盐，批号4.0，含量83.6%），均购于EDQM公司；杂质I（批号20190901，含量97.95%）购于深圳市恒丰万达医药科技有限公司；硫酸沙丁胺醇原料（批号1210105001）由山东京卫制药有限公司提供。
磷酸二氢钾（含量≥99.5%）、磷酸（含量≥85.0%）购自国药集团；庚烷磺酸钠（含量≥99.5%），购自山东禹王试剂；乙腈（纯度99.999%），购自Honeywell公司；超纯水（超纯水机），购自Merck Millipore公司。
国家药品抽检样品，共计110批，a企业39批，b企业32批，c企业5批，d企业34批。耐压铝罐包装。
2　方法与结果
收起
2.1　色谱条件
采用Thermo Syncronis C8色谱柱（250 mm×4.6 mm，5 μm），以庚烷磺酸钠溶液[取庚烷磺酸钠2.87 g与磷酸二氢钾2.5 g，加水溶解并稀释至1 000 mL，用磷酸溶液（用水稀释至2倍体积）调节pH至3.65]为流动相A，乙腈为流动相B，梯度洗脱（见表1），流速1.0 mL·min-1，柱温40 ℃，检测波长220 nm，进样体积20 μL。
2.2　溶液制备
2.2.1　供试品溶液
取样品1罐（规格20 mg），用乙醇将表面淋洗干净，温度10 min，取出，在铝盖上钻一小孔，插入注射针头（勿与液面接触），放至室温，轻轻摇动罐体，待抛射剂挥尽后（针头内无抛射剂继续喷出），约20~30 min，除去铝盖，加“2.1”项下流动相A-流动相B（80∶20）（简称溶剂），分次洗涤（洗涤3次，每次3 mL），合并洗液至50 mL量瓶中，用溶剂稀释至刻度，摇匀，即得。
2.2.2　杂质对照品储备溶液
取各杂质对照品适量，精密称定，分别用溶剂溶解并定量稀释制成每1 mL中约含20 μg的溶液，即得。
2.2.3　对照品储备溶液
取硫酸沙丁胺醇对照品和各杂质对照品适量，精密称定，用溶剂溶解并定量稀释制成每1 mL中约含5 μg的溶液，即得。
2.2.4　对照品溶液
取硫酸沙丁胺醇对照品和各杂质对照品适量，精密称定，用溶剂溶解并定量稀释制成每1 mL中约含0.4 μg的溶液，即得。
2.3　方法学验证
2.3.1　专属性试验
取生产企业提供的辅料（山东京卫制药有限公司提供空白辅料），照“2.2.2”项方法制备空白辅料溶液，按照“2.1”项方法测定，结果溶剂、辅料无干扰，专属性良好，见图1。
2.3.2　强制降解试验
通过分析合成工艺与可能的降解途径，采用强酸、强碱、氧化、光照、加热的方式对硫酸沙丁胺醇进行破坏性试验，采用建立的HPLC方法进行测定和研究，综合分析各种可能条件和降解途径产生的杂质。
取样品1罐，将内容物转移至50 mL量瓶中。（1）酸破坏：原料中加入1 mol·L-1盐酸溶液2 mL，60 ℃水浴中加热3 h后，加入1 mol·L-1氢氧化钠溶液2 mL碱中和，用溶剂定容至50 mL；（2）碱破坏：原料中加入5 mol·L-1氢氧化钠溶液2 mL，水浴（98~100 ℃）加热6 h后，加入5 mol·L-1盐酸溶液2 mL酸中和，用溶剂定容至50 mL；（3）氧化破坏：原料中加入30%过氧化氢溶液5 mL，80 ℃水浴加热氧化5 h后，放冷，用溶剂定容至50 mL；（4）加热破坏：原料中加入5 mL溶剂，水浴（98~100 ℃）加热6 h后，放冷，用溶剂定容至50 mL；（5）光照破坏：取原料48 mg，精密称定，置石英比色皿中，加入溶剂2 mL，置紫外灯下照射48 h。精密量取1 mL置50 mL量瓶中，用溶剂定容至刻度。各种破坏试验的杂质变化情况见图2。
2.3.3　精密度试验
取对照品溶液，连续进样6次，计算各杂质峰面积的RSD。结果表明，硫酸沙丁胺醇和各杂质峰面积精密度试验RSD（n=6）为0.30%~1.7%，精密度良好。
2.3.4　线性关系、相对校正因子考察
取对照品储备溶液，逐级稀释为浓度约为0.05、0.1、0.25、0.4、1、1.5、2.5、5 μg·mL-1的对照品系列溶液注入液相色谱仪，记录色谱图，绘制质量浓度（如果对照品为盐，则只计算碱基）对其峰面积的回归曲线，以主成分回归直线斜率与杂质回归直线斜率的比计算校正因子。结果见表2。
2.3.5　定量限与检测限
取对照品溶液，依次稀释，分别进样。以信噪比≥10的浓度确定定量限质量浓度。以信噪比≥3的浓度确定检测限质量浓度，结果见表2。
2.3.6　回收率考察
取硫酸沙丁胺醇原料共9份，每份约20 mg，置50 mL量瓶中，分别加入杂质对照品储备溶液0.8、1.0、1.2 mL，作为80%、100%、120% 3个浓度水平回收率溶液，用溶剂稀释至刻度，摇匀，测定。用外标法测得原料中含有0.014%杂质D、0.024%杂质F、0.020%杂质N，表中测得量已扣除本底量，除以加入量，计算回收率。结果见表3。
取空白辅料溶液9份，每份1.0 mL，置50 mL量瓶中，分别加入杂质对照品储备溶液0.8、1.0、1.2 mL，作为80%、100%、120% 3个浓度水平的回收率溶液，用溶剂稀释至刻度，摇匀，测定。测得量除以加入量，计算回收率。结果见表3。
2.3.7　耐用性试验
分别采用适当调整梯度、更换安捷伦1260高效液相色谱仪的方式进行耐用性试验。试验结果表明，在各试验条件下均能满足系统适用性要求，说明该方法耐用性良好。结果见表4。
2.4　样品的测定
按本文建立的方法测定4家生产企业的硫酸沙丁胺醇吸入气雾剂样品，杂质E、G、H均未检出，其它已知杂质及检出频次较高的未知杂质检出情况见表5，已知杂质测定结果的柱形散点图见图3。
3　讨论
收起
3.1　波长选择
2020年版《中国药典》二部中硫酸沙丁胺醇[14]有关物质的检测的波长为220 nm，通过二极管阵列检测器光谱扫描，由各峰吸收光谱可知硫酸沙丁胺醇、杂质A、杂质B、杂质C、杂质D、杂质E、杂质F、杂质H、杂质I、杂质N在220 nm附近有最大吸收或次大吸收，杂质G和杂质J在此波长也具有较大吸收，因此选定220 nm作为测定波长。
3.2　强制降解试验产生杂质分析
在文中试验条件下，加热、光照情况下比较稳定，产生的降解物较少，但对酸、氧化更为敏感。在酸情况下，杂质D、杂质F、杂质N显著增加。在碱情况下，杂质D、杂质I、杂质N增加较为明显，RRT 0.51、RRT 0.72处出现未知杂质。氧化情况下，杂质D、杂质J增加较为明显，RRT 1.23处出现大的未知杂质。光照条件下，杂质D、杂质N、杂质F略有增加。热破坏条件下，杂质D、杂质F略有增加。杂质A、杂质B、杂质C、杂质E、杂质G和杂质H等均没有增加，推测是工艺杂质。结果见表6。
3.3　样品检测结果分析
各企业样品检测结果均合格，杂质C、杂质D、杂质F、杂质N和未知杂质RRT 3.28检出频次较高，另外a企业中杂质A、RRT 0.88和RRT 5.84，b企业中杂质B、RRT 1.90，d企业中杂质I、RRT 0.54、RRT 0.59、RRT 0.70、RRT 1.32、RRT 2.42和RRT 5.76检出频次较高。均未检出杂质E、杂质G、杂质H，仅1批次检出杂质J。
从柱形散点图可知，a企业、d企业检出杂质的分布区间较小，而b企业分布区间较大，说明a企业、d企业生产制剂的工艺比b企业更可控。
国内有3家企业生产硫酸沙丁胺醇原料药，一般是溴代苯乙酮衍生物和胺发生取代反应，硼氢化钠还原羰基，生成4-苄基沙丁胺醇（杂质I），然后在Pd/C作用下生成沙丁胺醇。沙丁胺醇在甲醇或无水乙醇、乙酸乙酯溶剂中与硫酸成盐，生成硫酸沙丁胺醇。a企业产品处方除原料药、四氟乙烷134A外，不含其它辅料。b企业、c企业处方均使用原料药、四氟乙烷134A、无水乙醇、油酸；d企业使用大豆磷脂酰胆碱替代油酸。各企业工艺基本一致，原料药经微粉化，与辅料调剂后，直接灌装。因收集的资料不详细，无法推测各企业检出杂质与原料药、制剂处方工艺之间的明确对应关系。
3.4　杂质遗传毒性分析
参考2020年版《中国药典》9306遗传毒性杂质控制指导原则[15]、ICH M7（R2）[16]和欧洲药典委员会发布的基因毒性杂质结构警示[17]，硫酸沙丁胺醇可能含有的杂质中有多个带有N-羟甲基衍生物、芳香醛结构的遗传毒性致癌性警示结构。采用Derek Nexus 6.1.1（Lhasa公司，数控库Derek KB 2020，版本1.0）和 Sarah Nexus 3.1.1（Lhasa公司，模型Sarah Model -2020，版本1.8）对上述杂质进行遗传毒性（致突变性）进行预测，杂质D含有烷基醛(Aldehyde)结构，按ICH M7分类为2类，其余杂质为5类，后续应对杂质D应进行进一步的毒性研究，并确定合理的限度。评价结果请见表7。
4　结论
收起
本文制定的HPLC方法能准确地测定硫酸沙丁胺醇原料及吸入气雾剂中的常见有关物质，并给出各杂质的相对校正因子，分析了各杂质生成的可能途径和遗传基因毒性。该方法专属性强，灵敏度高，为该原料药及制剂的质量可控提供了准确的检验方法，为科学监管提供了有效的技术支持。采用新方法对国家药品评价抽验样品的有关物质进行了评价，结果均符合规定。
基金
收起
  • *泰山产业领军人才工程专项经费(tscx202306073)
文献
收起
参考文献 引证文献
排序方式：
[1]
张雪梅. 左旋硫酸沙丁胺醇肺部吸入给药的制剂与药效与作用研究[D]. 广州：华南理工大学，2013
ZHANG XM. The Study on Preparation and Pharmacodynamics of R-Salbutamol Sulfate for Pulmonary Inhalation[D]. Guangzhou：South China University of Technology，2013
[2]
KHALE A，BAJAJ A. Formulation and development of metered dose inhalations of salbutamol in solution form[J]. Indian J Pharm Sci，2012，73(5)：543
[3]
郑丹红. 硫酸沙丁胺醇雾化吸入治疗支气管哮喘急性发作的效果观察及护理[J]. 海峡药学，2011，23(11)：116
ZHENG DH. Observation and nursing of the effect of nebulized inhalation of salbutamol sulfate in the treatment of acute attacks of bronchial asthma[J]. Strait Pharm J，2011，23(11)：116
[4]
国家食品药品监督管理局药品审评中心. 四川美康医药软件研究开发有限公司. 药物临床信息参考[M]. 成都：四川科学技术出版社，2004：495
Center for Drug Evaluation，CFDA. Sichuan Medicom Software Co.，LTD. Clinical Drug Reference[M]. Chengdu：Sichuan Publishing House of Science & Technology，2004：495
[5]
莫建容，黄念华，黎小华. 硫酸沙丁胺醇气雾剂吸入与茶碱控释片治疗急性老年哮喘的临床疗效[J]. 中国医药科学，2018，8(12)：55
MO JR，HUANG NH，LI XH. Clinical efficacy of salbutamol sulfate aerosol inhalation and theophylline controlled release tablets in the treatment of acute senile asthma[J]. Chin Med Pharm，2018，8(12)：55
[6]
王枫，兰莉，乔艳梅. 硫酸沙丁胺醇联合氨茶碱治疗小儿哮喘的疗效观察[J]. 现代药物与临床，2017，32(9)：1683
WANG F，LAN L，QIAO YM. Clinical observation of salbutamol sulfate combined with aminophylline in treatment of children with asthma[J]. Drugs Clin，2017，32(9)：1683
[7]
梁利红，许丽萍，梁东阁，等. 小儿定喘口服液联合硫酸沙丁胺醇治疗小儿轻中度支气管哮喘的临床研究[J]. 现代药物与临床，2024，39(3)：680
LIANG LH，XU LP，LIANG DG，et al. Clinical study on Xiao’er Dingchuan oral liquid combined with salbutamol[J]. Drug Clin，2024，39(3)：680
[8]
仇中选，王东，管丽君，等. 硫酸沙丁胺醇有关物质的合成[J]. 中国医药工业杂志，2023，54(4)：540
QIU ZX，WANG D，GUAN LJ，et al. Synthesis of the related substances of salbutamol sulfate[J]. Chin J Pharm，2023，54(4)：540
[9]
叶小辉，孙宁云，戴健，等. 一种沙丁胺醇杂质的制备方法及应用：中国，112979480 B[P]. 2023-05-16
YE XH，SUN NY，DAI J，et al. A Preparation Method and Application of Impurities in Salbutamol：China，112979480 B[P]. 2023-05-16
[10]
EP 11[S]. 2022：3936
[11]
王鑫，刘宏大，薛雁，等. 高效液相色谱法测定硫酸沙丁胺醇有关物质的含量[J]. 安徽医药，2020，24(2)：242
WANG X，LIU HD，XUE Y，et al. HPLC method was used to determine the content of albuterol sulfate[J]. Anhui Med Pharm J，2020，24(2)：242
[12]
张冬梅，牛冲，冷佳蔚. HPLC测定硫酸沙丁胺醇雾化吸入溶液有关物质方法的研究[J]. 食品与药品，2012，14(11)：416
ZHANG DM，NIU C，LENG JW. Determination of related substances in salbutamol sulfate nebules inhalation solution by HPLC[J]. Food Drug，2012，14(11)：416
[13]
左文坚，史欣. HPLC测定硫酸沙丁胺醇缓释片有关物质及含量[J]. 中国药学杂志，2002，37(7)：55
ZUO WJ，SHI X. Assay for the content and related substance of salbutamol sulfate sustained release tablets by HPLC[J]. Chin Pharm J，2002，37(7)：55
[14]
中华人民共和国药典2020年版. 二部[S]. 2020：1583
ChP 2020. Vol Ⅱ[S]. 2020：1583
[15]
中华人民共和国药典2020年版. 四部[S]. 2020：547
ChP 2020. Vol Ⅳ[S]. 2020：547
[16]
ICH. Harmonised Guideline M7(R2)：Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceutic to Limit Potential Carcinogenic Risk[EB/OL]. Geneva：ICH，2013[2023-04-03]. https://www.ich.org/page/multidisciplinary-guidelines
[17]
BENIGNI R，BOSSA C，TCHEREMENSKAIA O，et al. Development of Structural Alerts for the In Vivo Micronucleus Assay in Rodents[EB/OL]. Luxembourg：OPOCE，2009[2009-06-03]. https://publications.jrc.ec.europa.eu/repository/handle/JRC52274
2024年第44卷第12期
PDF下载
73
31
引用本文
BibTeX
文章信息
doi: 10.16155/j.0254-1793.2024-0227
  • 接收时间：2024-04-07
  • 首发时间：2026-03-13
  • 出版时间：2024-12-31
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2024-04-07
基金
*泰山产业领军人才工程专项经费(tscx202306073)
作者信息
    1.山东省食品药品检验研究院 国家药品监督管理局仿制药研究与评价重点实验室 山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台，济南 250101
    2. 山东京卫制药有限公司，泰安 271000
    3.济南市第五人民医院，济南 250022

通讯作者:

**潘相蜜　Tel：18668991066；E-mail：
徐玉文　Tel：13553158409；E-mail：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/ywfxzz/CN/10.16155/j.0254-1793.2024-0227
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62199257
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持