首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1240997646127648987, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1240997638351409170, articleNumber=null, orderNo=null, doi=10.16155/j.0254-1793.2024-0422, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1719244800000, receivedDateStr=2024-06-25, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773806495458, onlineDateStr=2026-03-18, pubDate=1740672000000, pubDateStr=2025-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773806495458, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773806495458, creator=13701087609, updateTime=1773806495458, updator=13701087609, issue=Issue{id=1240997638351409170, tenantId=1146029695717560320, journalId=1205117023404326918, year='2025', volume='45', issue='2', pageStart='181', pageEnd='360', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773806493604, creator=13701087609, updateTime=1773810140860, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241012936110560131, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1240997638351409170, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241012936110560132, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1240997638351409170, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=290, endPage=296, ext={EN=ArticleExt(id=1240997646454804711, articleId=1240997646127648987, tenantId=1146029695717560320, journalId=1205117023404326918, language=EN, title=Determination of residual solvent formic acid and cyanoacetic acid in tofacitinib citrate by HPLC, columnId=1206272757852074373, journalTitle=Chinese Journal of Pharmaceutical Analysis, columnName=Safety Monitoring, runingTitle=null, highlight=null, articleAbstract=
Objective:

To establish an HPLC method for the determination of residual solvent formic acid and cyanoacetic acid content in tofacitinib citrate.

Methods:

The separation was performed on a Waters Atlantis T3(250 mm×4.6 mm, 5 μm) column with a gradient elution of 0.02 mol·L-1 potassium dihydrogen phosphate (pH was adjusted to 2.5 with phosphoric acid) (A) - methanol (B) as the mobile phases. The flow rate was 0.5 mL·min-1 and the column temperature was 35 ℃. Detection wavelength was 210 nm.

Results:

Formic acid and cyanoacetic acid were well separated from the adjacent peaks (R>5). The linearity was good in the concentration ranges of 9.930-107.780 μg·mL-1 and 14.727-98.908 μg·mL-1 (r = 0.999 9, 0.999 8), respectively. The average recoveries (n=9) were 100.2% and 105.3%, with RSDs of 2.3% and 4.1%, respectively. The determination results of three batches of samples were 0.024%, 0.026%, 0.028% (cyanoacetic acid), respectively.

Conclusion:

The established method is proved to be suitable for the determination of formic acid and cyanoacetic acid in tofacitinib citrate.

, correspAuthors=Yan-nan GENG, Yu-juan JIANG, 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=Li-juan SHI, Guan-jun CHENG, Li WANG, Min XU, Hui LI, Nuo WU, Yan-nan GENG, Yu-juan JIANG), CN=ArticleExt(id=1240997648078000459, articleId=1240997646127648987, tenantId=1146029695717560320, journalId=1205117023404326918, language=CN, title=HPLC法测定枸橼酸托法替布中残留溶剂甲酸和氰乙酸含量, columnId=1206272758036623764, journalTitle=药物分析杂志, columnName=安全监测, runingTitle=null, highlight=null, articleAbstract=
目的：

建立HPLC法测定枸橼酸托法替布中残留溶剂甲酸和氰乙酸的含量。

方法：

采用Waters Atlantis T3（250 mm×4.6 mm，5 µm）色谱柱，以0.02 mol·L-1磷酸二氢钾溶液（用磷酸调pH 2.5）-甲醇为流动相，梯度洗脱，流速0.5 mL·min-1，柱温35 ℃，检测波长210 nm。

结果：

甲酸、氰乙酸与相邻峰分离度良好（R>5）；分别在9.930~107.780 µg·mL-1、14.727~98.908 µg·mL-1浓度内线性关系良好（r = 0.999 9、0.999 8）；平均回收率（n=9）分别为100.2%、105.3%，RSD分别为2.3%、4.1%。稳定性考察（18个月）3批枸橼酸托法替布中含氰乙酸0.024%、0.026%、0.028%。

结论：

经方法学验证，本法可用于枸橼酸托法替布中甲酸和氰乙酸的含量测定。

, correspAuthors=耿燕楠, 江玉娟, authorNote=null, correspAuthorsNote=
*耿燕楠　Tel：（0531）88251837；E-mail：
江玉娟　Tel：（0531）88251837；E-mail：
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=OefAWNiHpZgLWwAfkg7wBw==, magXml=ZLwmWpURXNWqKZWQTVcnCw==, pdfUrl=null, pdf=cSGJ+9lVFcsXwT82Zwyn5w==, pdfFileSize=1336707, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=kPX/Jhl4x5IGbRaBFDIimQ==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=fAOD0Q1wHt+qL7cuIdx7Xg==, mapNumber=null, authorCompany=null, fund=null, authors=

Tel：（0531）88251837；E-mail：

, authorsList=石丽娟, 程贯军, 王莉, 许敏, 李慧, 吴诺, 耿燕楠, 江玉娟)}, authors=[Author(id=1241033138944659513, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=shilijuan521@126.com, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1241033139095654462, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033138944659513, language=EN, stringName=Li-juan SHI, firstName=Li-juan, middleName=null, lastName=SHI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033139158569024, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033138944659513, language=CN, stringName=石丽娟, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东明仁福瑞达制药股份有限公司，济南 250104, bio={"content":"

Tel：（0531）88251837；E-mail：

"}, bioImg=null, bioContent=

Tel：（0531）88251837；E-mail：

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138680418340, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=1., ext=[AuthorCompanyExt(id=1241033138684612645, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China), AuthorCompanyExt(id=1241033138693001254, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东明仁福瑞达制药股份有限公司，济南 250104)])]), Author(id=1241033139263426629, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, 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=1241033139355701324, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033139263426629, language=EN, stringName=Guan-jun CHENG, firstName=Guan-jun, middleName=null, lastName=CHENG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033139452170323, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033139263426629, language=CN, stringName=程贯军, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东明仁福瑞达制药股份有限公司，济南 250104, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138680418340, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=1., ext=[AuthorCompanyExt(id=1241033138684612645, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China), AuthorCompanyExt(id=1241033138693001254, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东明仁福瑞达制药股份有限公司，济南 250104)])]), Author(id=1241033139527667799, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, 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=1241033139666079839, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033139527667799, language=EN, stringName=Li WANG, firstName=Li, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033139766743140, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033139527667799, language=CN, stringName=王莉, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东明仁福瑞达制药股份有限公司，济南 250104, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138680418340, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=1., ext=[AuthorCompanyExt(id=1241033138684612645, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China), AuthorCompanyExt(id=1241033138693001254, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东明仁福瑞达制药股份有限公司，济南 250104)])]), Author(id=1241033139846434919, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, 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=1241033139938709611, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033139846434919, language=EN, stringName=Min XU, firstName=Min, middleName=null, lastName=XU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033140060344432, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033139846434919, language=CN, stringName=许敏, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东明仁福瑞达制药股份有限公司，济南 250104, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138680418340, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=1., ext=[AuthorCompanyExt(id=1241033138684612645, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China), AuthorCompanyExt(id=1241033138693001254, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东明仁福瑞达制药股份有限公司，济南 250104)])]), Author(id=1241033140156813430, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, 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=1241033140261671039, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033140156813430, language=EN, stringName=Hui LI, firstName=Hui, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033140353945740, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033140156813430, language=CN, stringName=李慧, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, address=1.山东明仁福瑞达制药股份有限公司，济南 250104, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138680418340, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=1., ext=[AuthorCompanyExt(id=1241033138684612645, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China), AuthorCompanyExt(id=1241033138693001254, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东明仁福瑞达制药股份有限公司，济南 250104)])]), Author(id=1241033140446220435, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, 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=1241033140580438171, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033140446220435, language=EN, stringName=Nuo WU, firstName=Nuo, middleName=null, lastName=WU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=3, address=3. Kongjiang Senior High School, Shanghai 200093, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033140676907172, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033140446220435, language=CN, stringName=吴诺, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=3, address=3.上海市控江中学，上海 200093, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138843996208, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=3., ext=[AuthorCompanyExt(id=1241033138852384817, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138843996208, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3. Kongjiang Senior High School, Shanghai 200093, China), AuthorCompanyExt(id=1241033138856579122, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138843996208, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.上海市控江中学，上海 200093)])]), Author(id=1241033140777570479, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, orderNo=6, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=gynan123@163.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1241033140903399611, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033140777570479, language=EN, stringName=Yan-nan GENG, firstName=Yan-nan, middleName=null, lastName=GENG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, *, address=2. Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033141004062915, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033140777570479, language=CN, stringName=耿燕楠, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=2, *, address=2.山东中医药大学附属医院药学部，济南 250014, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138747527210, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=2., ext=[AuthorCompanyExt(id=1241033138755915819, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138747527210, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China), AuthorCompanyExt(id=1241033138760110124, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138747527210, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.山东中医药大学附属医院药学部，济南 250014)])]), Author(id=1241033141121503433, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, orderNo=7, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=jyj0325@163.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1241033141230555338, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033141121503433, language=EN, stringName=Yu-juan JIANG, firstName=Yu-juan, middleName=null, lastName=JIANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, *, address=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1241033141314441425, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, authorId=1241033141121503433, language=CN, stringName=江玉娟, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=1, *, address=1.山东明仁福瑞达制药股份有限公司，济南 250104, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1241033138680418340, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=1., ext=[AuthorCompanyExt(id=1241033138684612645, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China), AuthorCompanyExt(id=1241033138693001254, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东明仁福瑞达制药股份有限公司，济南 250104)])])], keywords=[Keyword(id=1241033141494796511, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, orderNo=1, keyword=tofacitinib citrate), Keyword(id=1241033141591265512, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, orderNo=2, keyword=solvent residue), Keyword(id=1241033141666762990, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, orderNo=3, keyword=formic acid), Keyword(id=1241033141876478202, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, orderNo=4, keyword=cyanoacetic acid), Keyword(id=1241033141943587070, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, orderNo=5, keyword=content determination), Keyword(id=1241033142014890244, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, orderNo=6, keyword=methodological validation), Keyword(id=1241033142102970632, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, orderNo=7, keyword=HPLC), Keyword(id=1241033142203633935, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, orderNo=1, keyword=枸橼酸托法替布), Keyword(id=1241033142291714326, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, orderNo=2, keyword=溶剂残留), Keyword(id=1241033142371406108, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, orderNo=3, keyword=甲酸), Keyword(id=1241033142467875111, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, orderNo=4, keyword=氰乙酸), Keyword(id=1241033142543372587, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, orderNo=5, keyword=含量测定), Keyword(id=1241033142652424498, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, orderNo=6, keyword=方法学验证), Keyword(id=1241033142753087802, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, orderNo=7, keyword=高效液相色谱)], refs=[Reference(id=1241033144338534797, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=37, issue=7, pageStart=1291, pageEnd=null, url=null, language=null, rfNumber=［1］, rfOrder=0, authorNames=张霞, 李宏, 张华铃, journalName=药物分析杂志, refType=null, unstructuredReference=张霞，李宏，张华铃，等．正相高效液相色谱法测定枸橼酸托法替尼原料及片剂中对映异构体［J］．药物分析杂志，2017，37（7）：1291, articleTitle=正相高效液相色谱法测定枸橼酸托法替尼原料及片剂中对映异构体, refAbstract=null), Reference(id=1241033144443392400, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=37, issue=7, pageStart=1291, pageEnd=null, url=null, language=null, rfNumber=［1］, rfOrder=1, authorNames=ZHANG X, LI H, ZHANG HL, journalName=Chin J Pharm Anal, refType=null, unstructuredReference=ZHANG X，LI H，ZHANG HL，et al．Determination of enantiomer in tofacitinib citrate bulk drug and tablets by normal-phase HPLC ［J］．Chin J Pharm Anal，2017，37（7）：1291, articleTitle=Determination of enantiomer in tofacitinib citrate bulk drug and tablets by normal-phase HPLC, refAbstract=null), Reference(id=1241033144552444305, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2022, volume=49, issue=6, pageStart=192, pageEnd=null, url=null, language=null, rfNumber=［2］, rfOrder=2, authorNames=刘永波, journalName=广东化工, refType=null, unstructuredReference=刘永波．HPLC法测定枸橼酸托法替布片的含量［J］．广东化工，2022，49（6）：192, articleTitle=HPLC法测定枸橼酸托法替布片的含量, refAbstract=null), Reference(id=1241033144686662039, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2022, volume=49, issue=6, pageStart=192, pageEnd=null, url=null, language=null, rfNumber=［2］, rfOrder=3, authorNames=LIU YB, journalName=Guangdong Chem Ind J, refType=null, unstructuredReference=LIU YB．Content determination of active ingredients in tofacitinib citrate tablets by HPLC ［J］．Guangdong Chem Ind J，2022，49（6）：192, articleTitle=Content determination of active ingredients in tofacitinib citrate tablets by HPLC, refAbstract=null), Reference(id=1241033144774742428, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2021, volume=46, issue=1, pageStart=33, pageEnd=null, url=null, language=null, rfNumber=［3］, rfOrder=4, authorNames=张婷, 郭颖昕, 陈伟燕, journalName=上海化工, refType=null, unstructuredReference=张婷，郭颖昕，陈伟燕，等．反相高效液相色谱测定枸橼酸托法替布有关物质的方法学研究［J］．上海化工，2021，46（1）：33, articleTitle=反相高效液相色谱测定枸橼酸托法替布有关物质的方法学研究, refAbstract=null), Reference(id=1241033144854434207, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2021, volume=46, issue=1, pageStart=33, pageEnd=null, url=null, language=null, rfNumber=［3］, rfOrder=5, authorNames=ZHANG T, GUO YX, CHEN WY, journalName=Shanghai Chem Ind J, refType=null, unstructuredReference=ZHANG T，GUO YX，CHEN WY，et al．Methodological study on the determination of related substances of tofacitinib citrate by reversed-phase high performance liquid chromatography ［J］．Shanghai Chem Ind J，2021，46（1）：33, articleTitle=Methodological study on the determination of related substances of tofacitinib citrate by reversed-phase high performance liquid chromatography, refAbstract=null), Reference(id=1241033144929931686, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2019, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=［4］, rfOrder=6, authorNames=吕佳徽, journalName=null, refType=null, unstructuredReference=吕佳徽．枸橼酸托法替尼的工艺优化及质量研究［D］．济南：山东大学，2019, articleTitle=枸橼酸托法替尼的工艺优化及质量研究, refAbstract=null), Reference(id=1241033145026400684, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2019, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=［4］, rfOrder=7, authorNames=LYU JH, journalName=null, refType=null, unstructuredReference=LYU JH．Synthesis Process Optimization and Quality Research of Tofacitinib Citrate ［D］．Jinan：Shandong University，2019, articleTitle=Synthesis Process Optimization and Quality Research of Tofacitinib Citrate, refAbstract=null), Reference(id=1241033145114481070, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=［5］, rfOrder=8, authorNames=ICH, journalName=null, refType=null, unstructuredReference=ICH．Q3A（R2）Impurities in New Drug Substances ［EB/OL］．（2006-10-25）［2024-04-28］．https://database.ich.org/sites/default/files/Q3A%28R2%29%20Guideline.pdf, articleTitle=Q3A（R2）Impurities in New Drug Substances, refAbstract=null), Reference(id=1241033145244504497, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=［6］, rfOrder=9, authorNames=ICH, journalName=null, refType=null, unstructuredReference=ICH．Q3C（R8）Residual Solvents Guideline ［EB/OL］．（2020-03-25）［2024-04-28］．https://database.ich.org/sites/default/files/ICH_Q3C%28R9%29_Guideline_MinorRevision_2024_2024_Approved.pdf, articleTitle=Q3C（R8）Residual Solvents Guideline, refAbstract=null), Reference(id=1241033145366139317, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=116, pageEnd=null, url=null, language=null, rfNumber=［7］, rfOrder=10, authorNames=null, journalName=null, refType=null, unstructuredReference=中华人民共和国药典2020年版．四部［S］．2020：116, articleTitle=null, refAbstract=null), Reference(id=1241033145475191226, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=116, pageEnd=null, url=null, language=null, rfNumber=［7］, rfOrder=11, authorNames=null, journalName=null, refType=null, unstructuredReference=ChP 2020．Vol Ⅳ ［S］．2020：116, articleTitle=null, refAbstract=null), Reference(id=1241033145580048829, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2016, volume=26, issue=7, pageStart=489, pageEnd=null, url=null, language=null, rfNumber=［8］, rfOrder=12, authorNames=钟宝欣, 向以东, 宋世丘, journalName=今日药学, refType=null, unstructuredReference=钟宝欣，向以东，宋世丘．气相法测定头孢他啶原料药中甲酸残留的含量［J］．今日药学，2016，26（7）：489, articleTitle=气相法测定头孢他啶原料药中甲酸残留的含量, refAbstract=null), Reference(id=1241033145705877952, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2016, volume=26, issue=7, pageStart=489, pageEnd=null, url=null, language=null, rfNumber=［8］, rfOrder=13, authorNames=ZHONG BX, XIANG YD, SONG SQ, journalName=Pharm Today, refType=null, unstructuredReference=ZHONG BX，XIANG YD，SONG SQ．Determination of residual formic acid in ceftazidime pentahydrate bulk drug by gas chromatography ［J］．Pharm Today，2016，26（7）：489, articleTitle=Determination of residual formic acid in ceftazidime pentahydrate bulk drug by gas chromatography, refAbstract=null), Reference(id=1241033145827512771, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=26, issue=14, pageStart=14, pageEnd=null, url=null, language=null, rfNumber=［9］, rfOrder=14, authorNames=李超, journalName=中国药业, refType=null, unstructuredReference=李超．顶空毛细管气相色谱法测定克林霉素磷酸酯中甲酸残留量［J］．中国药业，2017，26（14）：14, articleTitle=顶空毛细管气相色谱法测定克林霉素磷酸酯中甲酸残留量, refAbstract=null), Reference(id=1241033145903010247, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=26, issue=14, pageStart=14, pageEnd=null, url=null, language=null, rfNumber=［9］, rfOrder=15, authorNames=LI C, journalName=China Pharm, refType=null, unstructuredReference=LI C．Determination of formic acid residue in clindamycin phosphate by headspace capillary gas chromatography［J］．China Pharm，2017，26（14）：14, articleTitle=Determination of formic acid residue in clindamycin phosphate by headspace capillary gas chromatography, refAbstract=null), Reference(id=1241033145986896331, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2009, volume=26, issue=5, pageStart=393, pageEnd=null, url=null, language=null, rfNumber=［10］, rfOrder=16, authorNames=马建兵, 郑学明, 尚会建, journalName=河北工业科技, refType=null, unstructuredReference=马建兵，郑学明，尚会建，等．氰乙酸的研究及应用［J］．河北工业科技，2009，26（5）：393, articleTitle=氰乙酸的研究及应用, refAbstract=null), Reference(id=1241033146062393805, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2009, volume=26, issue=5, pageStart=393, pageEnd=null, url=null, language=null, rfNumber=［10］, rfOrder=17, authorNames=MA JB, ZHENG XM, SHANG HJ, journalName=Hebei J Ind Sci Technol, refType=null, unstructuredReference=MA JB，ZHENG XM，SHANG HJ，et al．Research and application of cyanoacetic acid［J］．Hebei J Ind Sci Technol，2009，26（5）：393, articleTitle=Research and application of cyanoacetic acid, refAbstract=null), Reference(id=1241033146175640018, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2023, volume=50, issue=4, pageStart=61, pageEnd=null, url=null, language=null, rfNumber=［11］, rfOrder=18, authorNames=郑滔, 陈鹏, 汪华, journalName=云南化工, refType=null, unstructuredReference=郑滔，陈鹏，汪华，等．气相色谱法测定盐酸羟胺中甲酸［J］．云南化工，2023，50（4）：61, articleTitle=气相色谱法测定盐酸羟胺中甲酸, refAbstract=null), Reference(id=1241033146272109012, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2023, volume=50, issue=4, pageStart=61, pageEnd=null, url=null, language=null, rfNumber=［11］, rfOrder=19, authorNames=ZHENG T, CHEN P, WANG H, journalName=Yunnan Chem Ind J, refType=null, unstructuredReference=ZHENG T，CHEN P，WANG H，et al．Determination of formic acid in hydroxylamine hydrochloride by gas chromatograph［J］．Yunnan Chem Ind J，2023，50（4）：61, articleTitle=Determination of formic acid in hydroxylamine hydrochloride by gas chromatograph, refAbstract=null), Reference(id=1241033146364383704, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2023, volume=54, issue=6, pageStart=50, pageEnd=null, url=null, language=null, rfNumber=［12］, rfOrder=20, authorNames=姜艳玲, 赵敏, 李小宁, journalName=浙江化工, refType=null, unstructuredReference=姜艳玲，赵敏，李小宁，等．柱前衍生-气相色谱法测定非布司他残留溶剂甲酸的含量［J］．浙江化工，2023，54（6）：50, articleTitle=柱前衍生-气相色谱法测定非布司他残留溶剂甲酸的含量, refAbstract=null), Reference(id=1241033146460852702, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2023, volume=54, issue=6, pageStart=50, pageEnd=null, url=null, language=null, rfNumber=［12］, rfOrder=21, authorNames=JIANG YL, ZHAO M, LI XN, journalName=Zhejiang Chem Ind J, refType=null, unstructuredReference=JIANG YL，ZHAO M，LI XN，et al．Determination of residual solvent formic acid content in febuxostat by gas chromatography with pre-column derivatization［J］．Zhejiang Chem Ind J，2023，54（6）：50, articleTitle=Determination of residual solvent formic acid content in febuxostat by gas chromatography with pre-column derivatization, refAbstract=null), Reference(id=1241033146561516002, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2010, volume=38, issue=12, pageStart=197, pageEnd=null, url=null, language=null, rfNumber=［13］, rfOrder=22, authorNames=熊晓毅, 陈安群, 何咏梅, journalName=广州化工, refType=null, unstructuredReference=熊晓毅，陈安群，何咏梅．高效液相色谱测定氰乙酸的含量［J］．广州化工，2010，38（12）：197, articleTitle=高效液相色谱测定氰乙酸的含量, refAbstract=null), Reference(id=1241033146678956519, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2010, volume=38, issue=12, pageStart=197, pageEnd=null, url=null, language=null, rfNumber=［13］, rfOrder=23, authorNames=XIONG XY, CHEN AQ, HE YM, journalName=Guangzhou Chem Ind J, refType=null, unstructuredReference=XIONG XY，CHEN AQ，HE YM．Analysis of cyanoacetic acid content by HPLC［J］．Guangzhou Chem Ind J，2010，38（12）：197, articleTitle=Analysis of cyanoacetic acid content by HPLC, refAbstract=null), Reference(id=1241033146762842601, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=4, issue=16, pageStart=301, pageEnd=null, url=null, language=null, rfNumber=［14］, rfOrder=24, authorNames=陈宇, journalName=饮食保健, refType=null, unstructuredReference=陈宇．反相高效液相色谱法测定达托霉素溶液中残留溶剂甲酸、乙酸［J］．饮食保健，2017，4（16）：301, articleTitle=反相高效液相色谱法测定达托霉素溶液中残留溶剂甲酸、乙酸, refAbstract=null), Reference(id=1241033146850922993, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=4, issue=16, pageStart=301, pageEnd=null, url=null, language=null, rfNumber=［14］, rfOrder=25, authorNames=CHEN Y, journalName=Diet Health, refType=null, unstructuredReference=CHEN Y．Determination of residual solvents formic acid and acetic acid in daptomycin solution by reversed-phase HPLC［J］．Diet Health，2017，4（16）：301, articleTitle=Determination of residual solvents formic acid and acetic acid in daptomycin solution by reversed-phase HPLC, refAbstract=null), Reference(id=1241033146930614772, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2003, volume=21, issue=1, pageStart=57, pageEnd=null, url=null, language=null, rfNumber=［15］, rfOrder=26, authorNames=辛梅华, 李明春, 徐金瑞, journalName=环境工程, refType=null, unstructuredReference=辛梅华，李明春，徐金瑞，等．反相高效液相色谱法测定酸雨中的甲酸、乙酸、丙酸等 ［J］．环境工程，2003，21（1）：57, articleTitle=反相高效液相色谱法测定酸雨中的甲酸、乙酸、丙酸等, refAbstract=null), Reference(id=1241033147006112250, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2003, volume=21, issue=1, pageStart=57, pageEnd=null, url=null, language=null, rfNumber=［15］, rfOrder=27, authorNames=XIN MH, LI MC, XU JR, journalName=Environ Eng, refType=null, unstructuredReference=XIN MH，LI MC，XU JR，et al．Determination of formic acid，acetic acid and propionic acid in acid rain by reversed-phase HPLC ［J］．Environ Eng，2003，21（1）：57, articleTitle=Determination of formic acid，acetic acid and propionic acid in acid rain by reversed-phase HPLC, refAbstract=null), Reference(id=1241033147085804028, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=36, issue=5, pageStart=609, pageEnd=null, url=null, language=null, rfNumber=［16］, rfOrder=28, authorNames=许娟, 方芳, 陈云建, journalName=分析试验室, refType=null, unstructuredReference=许娟，方芳，陈云建，等．高效液相色谱法测定卡络磺钠中甲酸的残留量［J］．分析试验室，2017，36（5）：609, articleTitle=高效液相色谱法测定卡络磺钠中甲酸的残留量, refAbstract=null), Reference(id=1241033147186467328, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, doi=null, pmid=null, pmcid=null, year=2017, volume=36, issue=5, pageStart=609, pageEnd=null, url=null, language=null, rfNumber=［16］, rfOrder=29, authorNames=XU J, FANG F, CHEN YJ, journalName=Anal Lab, refType=null, unstructuredReference=XU J，FANG F，CHEN YJ，et al．Determination of formic acid residue in sodium carboxysulfonate by high performance liquid chromatography［J］．Anal Lab，2017，36（5）：609, articleTitle=Determination of formic acid residue in sodium carboxysulfonate by high performance liquid chromatography, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1241033138680418340, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=1., ext=[AuthorCompanyExt(id=1241033138684612645, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China), AuthorCompanyExt(id=1241033138693001254, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138680418340, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山东明仁福瑞达制药股份有限公司，济南 250104)]), AuthorCompany(id=1241033138747527210, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=2., ext=[AuthorCompanyExt(id=1241033138755915819, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138747527210, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China), AuthorCompanyExt(id=1241033138760110124, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138747527210, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.山东中医药大学附属医院药学部，济南 250014)]), AuthorCompany(id=1241033138843996208, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, xref=3., ext=[AuthorCompanyExt(id=1241033138852384817, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138843996208, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3. Kongjiang Senior High School, Shanghai 200093, China), AuthorCompanyExt(id=1241033138856579122, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, companyId=1241033138843996208, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.上海市控江中学，上海 200093)])], figs=[ArticleFig(id=1241033142971191621, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, label=Fig. 1, caption=Chromatograms of solvent (A), citric acid (B), referenc substance (C) and test solution (D), figureFileSmall=t+B2al1pDwuzYpTTXQkDlQ==, figureFileBig=bwDNwfH3oOWsyt08G7epSA==, tableContent=null), ArticleFig(id=1241033143055077705, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, label=图1, caption=溶剂（A）、枸橼酸（B）、对照品（C）和供试品溶液（D）色谱图

1.枸橼酸（citric acid）　2.甲酸（formic acid）　3.氰乙酸（cyaoace tic acid）　4.托法替布（tofacitinib）

, figureFileSmall=t+B2al1pDwuzYpTTXQkDlQ==, figureFileBig=bwDNwfH3oOWsyt08G7epSA==, tableContent=null), ArticleFig(id=1241033143176712529, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, label=Fig. 2, caption=Spectral index plots of formic acid and cyanoacetic acid, figureFileSmall=wMcGD2Oe5ZRViV06c03OHA==, figureFileBig=/Zcmrus/9RjrCsqMchx+LA==, tableContent=null), ArticleFig(id=1241033143277375832, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, label=图2, caption=甲酸及氰乙酸光谱指数图, figureFileSmall=wMcGD2Oe5ZRViV06c03OHA==, figureFileBig=/Zcmrus/9RjrCsqMchx+LA==, tableContent=null), ArticleFig(id=1241033143382233440, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, label=Tab. 1, caption=

Recovery test measurement results

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
（component）		加入量
（added）/µg		测得量
（measured）/µg		回收率
（recovery）/%		平均回收率
（average recovery）/%		RSD/%
甲酸（formic acid）269.450271.093100.698.62.5
269.450257.99495.8
269.450268.00899.5
538.900548.624101.8100.12.2
538.900543.630100.9
538.900526.17197.6
808.350823.774101.9101.81.4
808.350810.497100.3
808.350833.654103.1
氰乙酸（cyanoacetic acid）247.269253.595102.6108.65.7
247.269268.280108.5
247.269283.949114.83
494.538517.434104.63105.01.7
494.538529.316107.0
494.538511.108103.4
741.807754.050101.7102.20.90
741.807765.899103.3
741.807754.246101.7
), ArticleFig(id=1241033143499673959, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, label=表1, caption=

回收率试验测定结果（n=3）

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
（component）		加入量
（added）/µg		测得量
（measured）/µg		回收率
（recovery）/%		平均回收率
（average recovery）/%		RSD/%
甲酸（formic acid）269.450271.093100.698.62.5
269.450257.99495.8
269.450268.00899.5
538.900548.624101.8100.12.2
538.900543.630100.9
538.900526.17197.6
808.350823.774101.9101.81.4
808.350810.497100.3
808.350833.654103.1
氰乙酸（cyanoacetic acid）247.269253.595102.6108.65.7
247.269268.280108.5
247.269283.949114.83
494.538517.434104.63105.01.7
494.538529.316107.0
494.538511.108103.4
741.807754.050101.7102.20.90
741.807765.899103.3
741.807754.246101.7
), ArticleFig(id=1241033143625503084, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, label=Tab. 2, caption=

Durability test results

, figureFileSmall=null, figureFileBig=null, tableContent=
考察条件（conditions of investigation）分离度（resolution）
流速（flow rates）/（mL·min-1）0.45 5.63
0.50 5.64
0.55 6.03
流动相pH（mobile phase pH）2.34.03
2.57.99
2.76.36
柱温（column temperature）/℃30 5.34
355.63
40 5.64
色谱柱（column）批号（lot No.）01853027615.08
批号（lot No.）01663726515.29
), ArticleFig(id=1241033143717777773, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, label=表2, caption=

耐用性试验测定结果

, figureFileSmall=null, figureFileBig=null, tableContent=
考察条件（conditions of investigation）分离度（resolution）
流速（flow rates）/（mL·min-1）0.45 5.63
0.50 5.64
0.55 6.03
流动相pH（mobile phase pH）2.34.03
2.57.99
2.76.36
柱温（column temperature）/℃30 5.34
355.63
40 5.64
色谱柱（column）批号（lot No.）01853027615.08
批号（lot No.）01663726515.29
), ArticleFig(id=1241033143822635377, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, label=Tab. 3, caption=

Tofacitinib citrate influencing factors test examination test results

, figureFileSmall=null, figureFileBig=null, tableContent=
考察因素
（factor for examination）		时间
（time）/d		含量（content）/%
甲酸
（formic acid）		氰乙酸
（cyanoacetic acid）
光照试验（light test）0NDND
4 500 lx±500 lx5NDND
10NDND
20NDND
60 ℃高温试验（high-temperature test 60 ℃）0
5		ND
ND		ND
ND
10ND0.021
20ND0.019
高湿试验[high-humidity test（RH90%±5%）]0
5		ND
ND		ND
0.030
10ND0.025
20ND0.025
), ArticleFig(id=1241033143927492984, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, label=表3, caption=

枸橼酸托法替布影响因素试验考察试验结果

, figureFileSmall=null, figureFileBig=null, tableContent=
考察因素
（factor for examination）		时间
（time）/d		含量（content）/%
甲酸
（formic acid）		氰乙酸
（cyanoacetic acid）
光照试验（light test）0NDND
4 500 lx±500 lx5NDND
10NDND
20NDND
60 ℃高温试验（high-temperature test 60 ℃）0
5		ND
ND		ND
ND
10ND0.021
20ND0.019
高湿试验[high-humidity test（RH90%±5%）]0
5		ND
ND		ND
0.030
10ND0.025
20ND0.025
), ArticleFig(id=1241033144023961984, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=EN, label=Tab. 4, caption=

Long-term stability study of tofacitinib citrate（formic acid, cyanoacetic acid）test results

, figureFileSmall=null, figureFileBig=null, tableContent=
批号
（batch number）		时间（time）/月（month）含量（content）/%
甲酸
（formic acid）		氰乙酸
（cyanoacetic acid）
F14-21110013NDND
6NDND
12ND0.024
18ND0.026
F14-21100023NDND
6NDND
12NDND
18ND0.028
F14-21100013NDND
6NDND
12NDND
18ND0.018
), ArticleFig(id=1241033144128819587, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240997646127648987, language=CN, label=表4, caption=

枸橼酸托法替布长期稳定性考察（甲酸、氰乙酸）试验结果

, figureFileSmall=null, figureFileBig=null, tableContent=
批号
（batch number）		时间（time）/月（month）含量（content）/%
甲酸
（formic acid）		氰乙酸
（cyanoacetic acid）
F14-21110013NDND
6NDND
12ND0.024
18ND0.026
F14-21100023NDND
6NDND
12NDND
18ND0.028
F14-21100013NDND
6NDND
12NDND
18ND0.018
)], 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.0254-1793.2024-0422, detailUrlEn=https://castjournals.cast.org.cn/joweb/ywfxzz/EN/10.16155/j.0254-1793.2024-0422, pdfUrlCn=https://castjournals.cast.org.cn/joweb/ywfxzz/CN/PDF/10.16155/j.0254-1793.2024-0422, pdfUrlEn=https://castjournals.cast.org.cn/joweb/ywfxzz/EN/PDF/10.16155/j.0254-1793.2024-0422, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, reference=null)
收藏切换
HPLC法测定枸橼酸托法替布中残留溶剂甲酸和氰乙酸含量
收藏切换
PDF下载
石丽娟 1 , 程贯军 1 , 王莉 1 , 许敏 1 , 李慧 1 , 吴诺 3 , 耿燕楠 2, * , 江玉娟 1, *
药物分析杂志 | 安全监测 2025,45(2): 290-296
收起
收藏切换
药物分析杂志 | 安全监测 2025, 45(2): 290-296
HPLC法测定枸橼酸托法替布中残留溶剂甲酸和氰乙酸含量
全屏
石丽娟1 , 程贯军1, 王莉1, 许敏1, 李慧1, 吴诺3, 耿燕楠2, * , 江玉娟1, *
作者信息
  • 1.山东明仁福瑞达制药股份有限公司，济南 250104
  • 2.山东中医药大学附属医院药学部，济南 250014
  • 3.上海市控江中学，上海 200093

    • Tel：（0531）88251837；E-mail：

通讯作者:

*耿燕楠　Tel：（0531）88251837；E-mail：
江玉娟　Tel：（0531）88251837；E-mail：
Determination of residual solvent formic acid and cyanoacetic acid in tofacitinib citrate by HPLC
Li-juan SHI1 , Guan-jun CHENG1, Li WANG1, Min XU1, Hui LI1, Nuo WU3, Yan-nan GENG2, * , Yu-juan JIANG1, *
Affiliations
  • 1. Shandong Mingren Freda Pharm. Co., Ltd., Jinan 250104, China
  • 2. Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
  • 3. Kongjiang Senior High School, Shanghai 200093, China
出版时间: 2025-02-28 doi: 10.16155/j.0254-1793.2024-0422
文章导航
收藏切换
摘要
收起
目的：

建立HPLC法测定枸橼酸托法替布中残留溶剂甲酸和氰乙酸的含量。

方法：

采用Waters Atlantis T3（250 mm×4.6 mm，5 µm）色谱柱，以0.02 mol·L-1磷酸二氢钾溶液（用磷酸调pH 2.5）-甲醇为流动相，梯度洗脱，流速0.5 mL·min-1，柱温35 ℃，检测波长210 nm。

结果：

甲酸、氰乙酸与相邻峰分离度良好（R>5）；分别在9.930~107.780 µg·mL-1、14.727~98.908 µg·mL-1浓度内线性关系良好（r = 0.999 9、0.999 8）；平均回收率（n=9）分别为100.2%、105.3%，RSD分别为2.3%、4.1%。稳定性考察（18个月）3批枸橼酸托法替布中含氰乙酸0.024%、0.026%、0.028%。

结论：

经方法学验证，本法可用于枸橼酸托法替布中甲酸和氰乙酸的含量测定。

枸橼酸托法替布  /  溶剂残留  /  甲酸  /  氰乙酸  /  含量测定  /  方法学验证  /  高效液相色谱
Objective:

To establish an HPLC method for the determination of residual solvent formic acid and cyanoacetic acid content in tofacitinib citrate.

Methods:

The separation was performed on a Waters Atlantis T3(250 mm×4.6 mm, 5 μm) column with a gradient elution of 0.02 mol·L-1 potassium dihydrogen phosphate (pH was adjusted to 2.5 with phosphoric acid) (A) - methanol (B) as the mobile phases. The flow rate was 0.5 mL·min-1 and the column temperature was 35 ℃. Detection wavelength was 210 nm.

Results:

Formic acid and cyanoacetic acid were well separated from the adjacent peaks (R>5). The linearity was good in the concentration ranges of 9.930-107.780 μg·mL-1 and 14.727-98.908 μg·mL-1 (r = 0.999 9, 0.999 8), respectively. The average recoveries (n=9) were 100.2% and 105.3%, with RSDs of 2.3% and 4.1%, respectively. The determination results of three batches of samples were 0.024%, 0.026%, 0.028% (cyanoacetic acid), respectively.

Conclusion:

The established method is proved to be suitable for the determination of formic acid and cyanoacetic acid in tofacitinib citrate.

tofacitinib citrate  /  solvent residue  /  formic acid  /  cyanoacetic acid  /  content determination  /  methodological validation  /  HPLC
石丽娟, 程贯军, 王莉, 许敏, 李慧, 吴诺, 耿燕楠, 江玉娟. HPLC法测定枸橼酸托法替布中残留溶剂甲酸和氰乙酸含量. 药物分析杂志, 2025 , 45 (2) : 290 -296 . DOI: 10.16155/j.0254-1793.2024-0422
Li-juan SHI, Guan-jun CHENG, Li WANG, Min XU, Hui LI, Nuo WU, Yan-nan GENG, Yu-juan JIANG. Determination of residual solvent formic acid and cyanoacetic acid in tofacitinib citrate by HPLC[J]. Chinese Journal of Pharmaceutical Analysis, 2025 , 45 (2) : 290 -296 . DOI: 10.16155/j.0254-1793.2024-0422
正文
收起
枸橼酸托法替布（tofacitinib citrate）是由辉瑞（Pfizer）制药公司研发的治疗类风湿关节炎的创新药，是第1个被批准用于人类自免疫性疾病的JAK（Janus kinase）抑制剂，主要用于甲氨蝶呤治疗效果不佳或者对其不耐受的中重度活动性类风湿性关节患者[1-4]，能够有效缓解病情，降低药物的不良反应。
甲酸是枸橼酸托法替布合成工艺中使用的溶剂，可能存在残留，2020年版《中华人民共和国药典》四部残留溶剂测定法0861项下限度规定其含量不得过0.5%；氰乙酸为枸橼酸托法替布合成工艺中可能存在的降解杂质，对大鼠的口服LD50为1 500 mg·kg-1，毒性与甲酸接近（LD50=1 100 mg·kg-1，大鼠口服），对人体均有一定危害。基于此，本文以2020年版《中华人民共和国药典》四部、ICHQ3A和ICHQ3C指导原则为依据[5-7]，建立了枸橼酸托法替布中甲酸和氰乙酸检测方法，以便对其进行控制。
目前，原料药中残留溶剂甲酸的测定大多将甲酸衍生化后生成酯类物质，采用气相色谱法间接测得甲酸的残留量[8-9]，操作较为复杂；氰乙酸是1种有机合成中间体，多用于合成正丁酯医用黏合剂、维生素、巴比妥等原料药[10]，可能会有残余，国内尚未见同时测定枸橼酸托法替布中甲酸和氰乙酸含量的方法的报道。本文采用HPLC法,对枸橼酸托法替布中甲酸和氰乙酸含量进行测定，可以实现甲酸和氰乙酸2种杂质的同步控制，检测成本低，快速，为枸橼酸托法替布原料中甲酸和氰乙酸的检查提供了依据，也可为其他原料药中甲酸和氰乙酸的测定提供参考。
1　仪器与试药
收起
1.1　仪器
Waters ARC高效液相色谱仪，含Waters 2998 PDA检测器（Waters公司）；Agilent 1260高效液相色谱仪，含DAD检测器（安捷伦公司）；XPE205电子天平（绝对精度分度值达到0.01 mg，Mettler Toledo公司）；FA2004电子天平（绝对精度分度值达到0.1 mg，上海精密仪器有限公司）；S210酸度计（Mettler Toledo公司）；LHH-250SD药品稳定性试验箱（上海-恒科仪器有限公司）。
1.2　试药
甲醇、乙腈为分析纯，天津市康科德科技有限公司；磷酸为分析纯，天津富宇精细化工有限公司；磷酸二氢钾为分析纯，天津市大茂化学试剂厂；无水甲酸为分析纯，北京益利精细化学品有限公司；氰乙酸（98.22%），上海阿拉丁生化科技股份有限公司；盐酸为分析纯，烟台远东精细化工有限公司；纯净水，杭州娃哈哈集团有限公司；枸橼酸托法替布（批号F14-2110001、F14-2110002、F14-2111001），山东海佑福瑞达制药有限公司。
2　方法与结果
收起
2.1　色谱条件
采用Waters Atlantis T3（250 mm×4.6 mm，5 µm）色谱柱，以0.02 mol·L-1磷酸二氢钾溶液（用磷酸调节pH 2.5）为流动相A，以甲醇为流动相B，梯度洗脱（0~8 min，100%A；8~10 min，100%A→50%A；10~25 min，50%A；25~30 min，50%A→100%A；30~45 min，100%A），柱温35 ℃，检测波长210 nm，流速0.5 mL·min-1，进样体积10 µL。
2.2　溶液的制备
2.2.1　溶剂
0.1 mol·L-1盐酸溶液（取盐酸9 mL，用水稀释至1 000 mL）。
2.2.2　甲酸、氰乙酸储备液
称取无水甲酸、氰乙酸各适量，精密称定，分别加溶剂溶解并稀释成每1 mL中约含甲酸、氰乙酸各0.5 mg的溶液，摇匀，即得。
2.2.3　对照品溶液
精密量取甲酸、氰乙酸储备液各1 mL，置10 mL量瓶中，加溶剂稀释至刻度，摇匀，即得。
2.2.4　甲酸、氰乙酸定位溶液
精密量取甲酸、氰乙酸储备液各1 mL，分别置10 mL量瓶中，加溶剂稀释至刻度，摇匀，即得。
2.2.5　供试品溶液
取枸橼酸托法替布适量，精密称定，加溶剂溶解并稀释成每1 mL中约含枸橼酸托法替布10 mg的溶液，摇匀，即得。
2.2.6　枸橼酸定位溶液
取枸橼酸一水合物适量，加溶剂溶解并稀释成每1 mL中约含枸橼酸4 mg的溶液，摇匀，即得。
2.2.7　混合线性储备液
取无水甲酸、氰乙酸适量，精密称定，加溶剂溶解并稀释成每1 mL中约含甲酸、氰乙酸0.5 mg的溶液，摇匀，即得。
2.3　方法学考察
2.3.1　系统适用性及专属性试验
取“2.2”项下溶剂，对照品溶液，甲酸、氰乙酸定位溶液，供试品溶液，枸橼酸定位溶液各10 µL，按“2.1”项下色谱条件进行测定，其中对照品溶液连续进样6次，记录色谱图并计算结果。结果显示，空白溶剂、枸橼酸、枸橼酸托法替布均不干扰甲酸、氰乙酸的检测，对照品溶液图谱中，甲酸峰和氰乙酸峰的分离度为5.63（见图1），本方法专属性良好；对照品溶液连续进样6次，甲酸、氰乙酸峰面积的RSD分别为1.2%、1.9%，表明系统适用性良好。
2.3.2　溶液稳定性试验
取“2.2.3”和“2.2.5”项下配制的对照品溶液及供试品溶液，于室温放置，分别于第0、2、4、6、7、12及24 h，按“2.1”项下色谱条件进行测定，记录色谱图。结果供试品溶液中12 h内均未检出甲酸和氰乙酸，表明供试品溶液在室温下放置12 h稳定；对照品溶液中24 h内甲酸峰和氰乙酸峰面积的RSD分别为1.0%、2.1%，表明对照品溶液在室温下放置24 h稳定。
2.3.3　重复性试验
按“2.2.5”项下方法，配制6份供试品溶液。精密量取10 µL，分别注入液相色谱仪，记录色谱图，结果6次测定均未检出甲酸、氰乙酸，表明本方法重复性良好。
2.3.4　中间精密度试验
按“2.1”项下方法，不同实验人员于不同的时间采用不同仪器，分别平行测定6份供试品的甲酸、氰乙酸。结果表明，同一批次样品2组12次试验均未检出甲酸、氰乙酸，表明中间精密度较好。
2.3.5　定量限及检测限
取“2.2.2”项下甲酸储备液、氰乙酸储备液适量，用溶剂稀释成系列溶液，分别进样分析。以信噪比S/N≈10时所对应的浓度为定量限，测得甲酸、氰乙酸的定量限分别为9.930、14.727 µg·mL-1；以S/N≈3时所对应的浓度为检测限，测得甲酸、氰乙酸的检测限分别为2.979、4.418 µg·mL-1。定量限连续进样6针，甲酸、氰乙酸峰面积的RSD分别为7.0%、3.5%，表明甲酸、氰乙酸定量限溶液精密度良好。
2.3.6　线性关系考察
精密量取“2.3.5”项下定量限溶液作为线性系列溶液1#；精密量取“2.2.7”项下混合线性储备液，用溶剂分别稀释制成不同浓度系列溶液2#~5#，按“2.1”项下色谱条件进样测定，记录色谱图。以质量浓度C为横坐标，峰面积A为纵坐标绘制标准曲线，计算得甲酸和氰乙酸回归方程：

A = 1 151.2C - 1 402.7　 r = 0.999 9

A = 628.22C - 955.28　 r = 0.999 8

质量浓度分别在9.930~107.780 µg·mL-1、14.727~98.908 µg·mL-1范围内与峰面积线性关系良好。
2.3.7　回收率试验
称取枸橼酸托法替布（批号F14-2110001）约100 mg，精密称定，置10 mL量瓶中，共9份，精密加入“2.2.7”项下混合线性储备液0.5、1.0、1.5 mL，各3份，用溶剂稀释为50%供试溶液（1#~3#）、100%供试溶液（4#~6#）、150%供试溶液（7#~9#），进样测定，结果见表1，本方法准确度良好。
2.3.8　耐用性试验
取同一批样品和对照品，改变流速（±0.05 mL·min-1）、柱温（±5 ℃）、流动相pH（±0.2）及不同批号色谱柱，考察系统适用性及甲酸、氰乙酸检出量。结果表明，上述条件改变下的样品中甲酸、氰乙酸均无变化；对照品中甲酸和氰乙酸分离度在4.03~7.99，耐用性良好。见表2。
2.3.9　样品测定结果及影响降解因素考察
3批样品（批号F14-2110001、F14-2110002、F14-2111001）中均未检出甲酸和氰乙酸。取批号为F14-2110001的样品，通过影响因素试验考察甲酸和氰乙酸含量（见表3），结果表明氰乙酸为枸橼酸托法替布的降解产物，对高温、高湿条件较为敏感，需对其进行测定分析，以便更好地监控枸橼酸托法替布的质量。
2.3.10　枸橼酸托法替布长期稳定性考察（甲酸、氰乙酸）
枸橼酸托法替布贮存于稳定性试验箱（30 ℃±2 ℃；RH65%±5%），3批样品（F14-2110001、F14-2110002、F14-2111001）长期稳定性试验考察发现，随着时间推移，氰乙酸含量逐渐上升，详见表4。表明氰乙酸为枸橼酸托法替布的降解产物，需对其含量进行测定，以完善枸橼酸托法替布的质量控制。
3　讨论
收起
3.1　检测方法及色谱条件的选择
3.1.1　检测方法
甲酸气化性能不良，色谱峰拖尾严重，保留时间也较长，无法直接检出，应用GC法需将甲酸转化为甲酸乙酯，再计算甲酸含量，操作烦琐，采用HPLC法进行甲酸和氰乙酸的检测，与GC法对比，具有操作简单、成本低等优点[11-12]。
3.1.2　检测波长
采用二极管阵列检测器（DAD）对甲酸和氰乙酸在190~400 nm波长范围内进行光谱扫描，并记录吸收曲线（见图2），甲酸的最大吸收波长为206.8 nm，氰乙酸无特征吸收，但甲酸和氰乙酸均有明显的末端吸收，故确定甲酸、氰乙酸检测波长为210 nm。
3.1.3　色谱柱
参考相关文献[13-16]，首先采用ZORBAX SB-C18（250 mm×4.6 mm，5 µm）色谱柱进样分析，发现溶剂峰影响甲酸和氰乙酸的分离；另外采用Sunniest SB-C18（250 mm×4.6 mm，5 µm）色谱柱，甲酸和氰乙酸分离度较差，无法满足要求（R<1.5）；考虑甲酸和氰乙酸极性较大，增强其保留值为方法开发的主要关键点之一，故采用亲水性Waters Atlantis T3（250 mm×4.6 mm，5 µm）色谱柱，保留能力强于ZOBAX SB-C18色谱柱，可以更好地分离目标物。通过对比不同亲水色谱柱，最终确定采用Waters Atlantis T3（250 mm×4.6 mm，5 µm）色谱柱。
3.1.4　流动相体系
考察了以0.02 mol·L-1磷酸二氢钾溶液为流动相A，分别以甲醇、乙腈为流动相B，结果表明采用乙腈峰形对称性差；考察了0.02 mol·L-1磷酸二氢钾溶液（磷酸调pH 2.3~3.0），并以甲醇为流动相B，同时优化梯度洗脱程序，最终确定以0.02 mol·L-1磷酸二氢钾溶液（磷酸调pH=2.5）为流动相A，以甲醇为流动相B，进行梯度洗脱，峰形对称且分离效果良好。
3.1.5　色谱柱温度
调节色谱柱温度为30、35、40 ℃，考察温度对甲酸和氰乙酸分离度的影响，其分离度分别为7.16、6.48、5.61，柱温对目标峰分离度影响较小，综合考虑柱温对柱效的影响，确定35 ℃为检测温度。
3.2　方法的评价
本试验采用HPLC技术建立了同时测定枸橼酸托法替布中甲酸和氰乙酸含量的测定方法，避免了气相色谱测定的样品衍生化处理的复杂步骤，重现性好，灵敏度高，检测成本低，能快速准确地测定枸橼酸托法替布中甲酸和氰乙酸的含量。参考2020年版《中华人民共和国药典》，对该方法进行了方法学验证，结果该方法的专属性、线性、检测限和定量限、精密度、回收率均符合验证要求，同时进行耐用性研究，考察既定的色谱条件发生微小变动，对方法适用性的影响，确定色谱条件的适用范围，本方法适用于枸橼酸托法替布中甲酸和氰乙酸含量检测。
4　结论
收起
枸橼酸托法替布中的残留溶剂甲酸和降解杂质氰乙酸均具有毒性，对人体造成伤害。通过对比市场上不同厂家原料，发现原料质量参差不齐，本实验采用HPLC技术，建立了同时测定枸橼酸托法替布中甲酸和氰乙酸含量的检测方法，该方操作简单，成本低，能够为枸橼酸托法替布中甲酸、氰乙酸的含量测定提供依据，为其他产品中甲酸、氰乙酸的测定提供参考。
文献
收起
参考文献 引证文献
排序方式：
［1］
张霞，李宏，张华铃，等．正相高效液相色谱法测定枸橼酸托法替尼原料及片剂中对映异构体［J］．药物分析杂志，2017，37（7）：1291
ZHANG X，LI H，ZHANG HL，et al．Determination of enantiomer in tofacitinib citrate bulk drug and tablets by normal-phase HPLC ［J］．Chin J Pharm Anal，2017，37（7）：1291
［2］
刘永波．HPLC法测定枸橼酸托法替布片的含量［J］．广东化工，2022，49（6）：192
LIU YB．Content determination of active ingredients in tofacitinib citrate tablets by HPLC ［J］．Guangdong Chem Ind J，2022，49（6）：192
［3］
张婷，郭颖昕，陈伟燕，等．反相高效液相色谱测定枸橼酸托法替布有关物质的方法学研究［J］．上海化工，2021，46（1）：33
ZHANG T，GUO YX，CHEN WY，et al．Methodological study on the determination of related substances of tofacitinib citrate by reversed-phase high performance liquid chromatography ［J］．Shanghai Chem Ind J，2021，46（1）：33
［4］
吕佳徽．枸橼酸托法替尼的工艺优化及质量研究［D］．济南：山东大学，2019
LYU JH．Synthesis Process Optimization and Quality Research of Tofacitinib Citrate ［D］．Jinan：Shandong University，2019
［5］
ICH．Q3A（R2）Impurities in New Drug Substances ［EB/OL］．（2006-10-25）［2024-04-28］．https://database.ich.org/sites/default/files/Q3A%28R2%29%20Guideline.pdf
［6］
ICH．Q3C（R8）Residual Solvents Guideline ［EB/OL］．（2020-03-25）［2024-04-28］．https://database.ich.org/sites/default/files/ICH_Q3C%28R9%29_Guideline_MinorRevision_2024_2024_Approved.pdf
［7］
中华人民共和国药典2020年版．四部［S］．2020：116
ChP 2020．Vol Ⅳ ［S］．2020：116
［8］
钟宝欣，向以东，宋世丘．气相法测定头孢他啶原料药中甲酸残留的含量［J］．今日药学，2016，26（7）：489
ZHONG BX，XIANG YD，SONG SQ．Determination of residual formic acid in ceftazidime pentahydrate bulk drug by gas chromatography ［J］．Pharm Today，2016，26（7）：489
［9］
李超．顶空毛细管气相色谱法测定克林霉素磷酸酯中甲酸残留量［J］．中国药业，2017，26（14）：14
LI C．Determination of formic acid residue in clindamycin phosphate by headspace capillary gas chromatography［J］．China Pharm，2017，26（14）：14
［10］
马建兵，郑学明，尚会建，等．氰乙酸的研究及应用［J］．河北工业科技，2009，26（5）：393
MA JB，ZHENG XM，SHANG HJ，et al．Research and application of cyanoacetic acid［J］．Hebei J Ind Sci Technol，2009，26（5）：393
［11］
郑滔，陈鹏，汪华，等．气相色谱法测定盐酸羟胺中甲酸［J］．云南化工，2023，50（4）：61
ZHENG T，CHEN P，WANG H，et al．Determination of formic acid in hydroxylamine hydrochloride by gas chromatograph［J］．Yunnan Chem Ind J，2023，50（4）：61
［12］
姜艳玲，赵敏，李小宁，等．柱前衍生-气相色谱法测定非布司他残留溶剂甲酸的含量［J］．浙江化工，2023，54（6）：50
JIANG YL，ZHAO M，LI XN，et al．Determination of residual solvent formic acid content in febuxostat by gas chromatography with pre-column derivatization［J］．Zhejiang Chem Ind J，2023，54（6）：50
［13］
熊晓毅，陈安群，何咏梅．高效液相色谱测定氰乙酸的含量［J］．广州化工，2010，38（12）：197
XIONG XY，CHEN AQ，HE YM．Analysis of cyanoacetic acid content by HPLC［J］．Guangzhou Chem Ind J，2010，38（12）：197
［14］
陈宇．反相高效液相色谱法测定达托霉素溶液中残留溶剂甲酸、乙酸［J］．饮食保健，2017，4（16）：301
CHEN Y．Determination of residual solvents formic acid and acetic acid in daptomycin solution by reversed-phase HPLC［J］．Diet Health，2017，4（16）：301
［15］
辛梅华，李明春，徐金瑞，等．反相高效液相色谱法测定酸雨中的甲酸、乙酸、丙酸等 ［J］．环境工程，2003，21（1）：57
XIN MH，LI MC，XU JR，et al．Determination of formic acid，acetic acid and propionic acid in acid rain by reversed-phase HPLC ［J］．Environ Eng，2003，21（1）：57
［16］
许娟，方芳，陈云建，等．高效液相色谱法测定卡络磺钠中甲酸的残留量［J］．分析试验室，2017，36（5）：609
XU J，FANG F，CHEN YJ，et al．Determination of formic acid residue in sodium carboxysulfonate by high performance liquid chromatography［J］．Anal Lab，2017，36（5）：609
2025年第45卷第2期
PDF下载
95
43
引用本文
BibTeX
文章信息
doi: 10.16155/j.0254-1793.2024-0422
  • 接收时间：2024-06-25
  • 首发时间：2026-03-18
  • 出版时间：2025-02-28
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2024-06-25
基金
作者信息
    1.山东明仁福瑞达制药股份有限公司，济南 250104
    2.山东中医药大学附属医院药学部，济南 250014
    3.上海市控江中学，上海 200093

通讯作者:

*耿燕楠　Tel：（0531）88251837；E-mail：
江玉娟　Tel：（0531）88251837；E-mail：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/ywfxzz/CN/10.16155/j.0254-1793.2024-0422
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