首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1193877805848035790, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1193877800143777917, articleNumber=1001-2494(2025)02-0184-05, orderNo=null, doi=10.11669/cpj.2025.02.011, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1716912000000, receivedDateStr=2024-05-29, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1762572250090, onlineDateStr=2025-11-08, pubDate=1737475200000, pubDateStr=2025-01-22, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762572250090, onlineIssueDateStr=2025-11-08, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762572250090, creator=13701087609, updateTime=1762572250090, updator=13701087609, issue=Issue{id=1193877800143777917, tenantId=1146029695717560320, journalId=1190317699101192196, year='2025', volume='60', issue='2', pageStart='109', pageEnd='206', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=0, articleOrder=1, issueType=-1, specialIssue=null, createTime=1762572248731, creator=13701087609, updateTime=1762584852274, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1193930663289123481, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1193877800143777917, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1193930663289123482, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1193877800143777917, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=184, endPage=188, ext={EN=ArticleExt(id=1193877806154219991, articleId=1193877805848035790, tenantId=1146029695717560320, journalId=1190317699101192196, language=EN, title=Quantitative Analysis of 1,2-Dioleoyl-sn-glycero-3-Phosphocholine in Pharmaceutical Excipients by Proton Nuclear Magnetic Resonance, columnId=null, journalTitle=Chinese Pharmaceutical Journal, columnName=null, runingTitle=null, highlight=null, articleAbstract=

OBJECTIVE To develop a quantitative proton nuclear magnetic resonance (qHNMR) method for the determination of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). METHODS A Bruker AVANCE Ⅱ 600 MHz NMR resonance spectra was utilized to acquire the NMR spectra of DOPC. The compound 1,3,5-trimethoxybenzene served as the internal standard, deuterated chloroform as the solvent, with 30° pulses, 16 scans, a test temperature of 25 ℃, and an acquisition time (AQ) of 5 s. The relaxation delay time (D1) was set at 35 s for quantitative analysis of DOPC. RESULTS The sample's 1H-NMR spectra displayed a methyl proton signal at chemical shift δ 0.87; the quantitative peak signals of DOPC and internal standard were well resolved on the 1H-NMR spectra with good linear relationship for DOPC (r>0.9996). The method demonstrated accuracy and repeatability with DOPC content ranging from 96.7% to 98.7%, consistent with results obtained from phosphomolybdic acid colorimetry. CONCLUSION The established qHNMR method accurately quantifies DOPC, is faster than the classical phosphomolybdate colometry method, requires no complex pretreatment operations.

, correspAuthors=Xuefan CHEN, 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=Yawen WANG, Xuefan CHEN), CN=ArticleExt(id=1193877946185253656, articleId=1193877805848035790, tenantId=1146029695717560320, journalId=1190317699101192196, language=CN, title=定量核磁共振氢谱法测定药用辅料二油酰基磷脂酰胆碱的含量, columnId=1190352405612040510, journalTitle=中国药学杂志, columnName=论著, runingTitle=null, highlight=null, articleAbstract=

目的 建立测定二油酰基磷脂酰胆碱(1,2-dioleoyl-SN-glycero-3-phosphocholine,DOPC)含量的定量核磁共振氢谱法(quantitative proton nuclear magnetic resonance, qHNMR)。方法 采用Bruker AVANCE Ⅱ 600 MHz核磁共振波谱仪,采集DOPC的核磁共振氢谱,以1,3,5-三甲氧基苯为内标物,氘代氯仿为溶剂,30°脉冲,扫描次数为16次,测试温度25 ℃,采集时间(AQ)为5 s,弛豫延迟时间(D1)为35 s,对DOPC进行定量分析。结果 样品的1H-NMR谱在化学位移δ 0.87出现甲基的质子信号,DOPC和内标物定量峰信号在1H-NMR谱上分离度良好,DOPC在线性范围内线性关系良好(r>0.999 6),方法精密度和重复性良好,DOPC含量为96.7%~98.7%,测定结果与磷钼酸比色法测定结果基本一致。结论 建立的qHNMR方法可以对DOPC进行准确定量,相比于经典的磷钼酸比色方法更加快速,并且不需要复杂的前处理操作。

, correspAuthors=陈雪帆, authorNote=null, correspAuthorsNote=
*陈雪帆,男,硕士,高级工程师 研究方向:药物分析 Tel:(0517)88871559
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=JEu8k60jTo0PUco46q9YEA==, magXml=SQbWfd6MTuQLYQ0WFz4iOA==, pdfUrl=null, pdf=96uDQLinB9wMEK3ojwznmg==, pdfFileSize=1243221, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=I/PYwT3YA0tbcOxN9wNbnQ==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=Q2wvUBlZmrY3MG+Bsfw35Q==, mapNumber=null, authorCompany=null, fund=null, authors=

王娅雯,女,硕士研究生 研究方向:药物分析

, authorsList=王娅雯, 陈雪帆)}, authors=[Author(id=1193928892265235101, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, orderNo=0, 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=1193928892323955358, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, authorId=1193928892265235101, language=EN, stringName=Yawen WANG, firstName=Yawen, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=null, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1193928892382675615, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, authorId=1193928892265235101, language=CN, stringName=王娅雯, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=null, bio={"content":"

王娅雯,女,硕士研究生 研究方向:药物分析

"}, bioImg=null, bioContent=

王娅雯,女,硕士研究生 研究方向:药物分析

, aboutCorrespAuthor=null)}, companyList=null), Author(id=1193928892445590177, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, 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=1, authorType=1, ext={EN=AuthorExt(id=1193928892521087650, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, authorId=1193928892445590177, language=EN, stringName=Xuefan CHEN, firstName=Xuefan, middleName=null, lastName=CHEN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=null, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1193928892579807907, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, authorId=1193928892445590177, language=CN, stringName=陈雪帆, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=null, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=null)], keywords=[Keyword(id=1193928892697248420, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, orderNo=1, keyword=quantitative nuclear magnetic resonance), Keyword(id=1193928892751774373, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, orderNo=2, keyword=pharmaceutical excipient), Keyword(id=1193928892802106022, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, orderNo=3, keyword=content determination), Keyword(id=1193928892852437671, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, orderNo=4, keyword=internal standard method), Keyword(id=1193928892915352232, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, orderNo=5, keyword=DOPC), Keyword(id=1193928892978266793, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, orderNo=1, keyword=定量核磁共振氢谱法), Keyword(id=1193928893041181354, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, orderNo=2, keyword=药用辅料), Keyword(id=1193928893095707307, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, orderNo=3, keyword=含量测定), Keyword(id=1193928893154427564, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, orderNo=4, keyword=内标法), Keyword(id=1193928893208953517, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, orderNo=5, keyword=二油酰基磷脂酰胆碱)], refs=[Reference(id=1193928894484021945, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2020, volume=12, issue=12, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=DRESCHER S, journalName=Pharmaceutics, refType=null, unstructuredReference=DRESCHER S, VAN HOOGEVEST P. The phospholipid research center: current research in phospholipids and their use in drug delivery[J]. Pharmaceutics, 2020, 12(12): 1235. DOI: 10.3390/pharmaceutics12121235., articleTitle=VAN HOOGEVEST P. The phospholipid research center: current research in phospholipids and their use in drug delivery, refAbstract=null), Reference(id=1193928894597268154, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2005, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=ZHANG Y Y, journalName=Study on the purification method of phosphatidylcholine with high content, refType=null, unstructuredReference=ZHANG Y Y. Study on the purification method of phosphatidylcholine with high content[D]. Hangzhou: Zhejiang University, 2005., articleTitle=null, refAbstract=null), Reference(id=1193928894664377019, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=null, journalName=null, refType=null, unstructuredReference=Suzhou South East Pharmaceuticals Co.,Ltd, Jiangsu Southeast Nano Materials Co.,Ltd. The invention discloses a preparation method for dioleoyl phosphatidylcholine: China, 201911092006. 5[P]. 2020-07-28., articleTitle=5, refAbstract=null), Reference(id=1193928894735680188, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2010, volume=27, issue=8, pageStart=1469, pageEnd=1486, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=FRICKER G, KROMP T, WENDEL A, journalName=Pharm Res, refType=null, unstructuredReference=FRICKER G, KROMP T, WENDEL A, et al. Phospholipids and lipid-based formulations in oral drug delivery[J]. Pharm Res, 2010, 27(8): 1469-1486., articleTitle=Phospholipids and lipid-based formulations in oral drug delivery, refAbstract=null), Reference(id=1193928894802789053, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2013, volume=436, issue=null, pageStart=434, pageEnd=442, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=YANG R, ZHANG X, LI F, journalName=Colloids Surf A, refType=null, unstructuredReference=YANG R, ZHANG X, LI F, et al. Role of phospholipids and copolymers in enhancing stability and controlling degradation of intravenous lipid emulsions[J]. Colloids Surf A, 2013, 436: 434-442., articleTitle=Role of phospholipids and copolymers in enhancing stability and controlling degradation of intravenous lipid emulsions, refAbstract=null), Reference(id=1193928894874092222, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2002, volume=41, issue=5, pageStart=392, pageEnd=406, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=MANTRIPRAGADA S, A lipid based depot, DepoFoam® technology, journalName=Prog Lipid Res, refType=null, unstructuredReference=MANTRIPRAGADA S. A lipid based depot ( DepoFoam® technology) for sustained release drug delivery[J]. Prog Lipid Res, 2002, 41 (5): 392-406., articleTitle=for sustained release drug delivery, refAbstract=null), Reference(id=1193928894949589695, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2021, volume=349, issue=null, pageStart=129082, pageEnd=null, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=KIM H, WOO Y, CHOI H, journalName=Food Chem, refType=null, unstructuredReference=KIM H, WOO Y, CHOI H, et al. Dioleylphosphatidylcholine increases the antioxidant properties of ascorbyl palmitate in bulk oils compared to other hydrophilic and lipophilic antioxidants[J]. Food Chem, 2021, 349: 129082. DOI: 10.1016/j.foodchem.2021.129082, articleTitle=Dioleylphosphatidylcholine increases the antioxidant properties of ascorbyl palmitate in bulk oils compared to other hydrophilic and lipophilic antioxidants, refAbstract=null), Reference(id=1193928895025087168, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2020, volume=25, issue=21, pageStart=5128, pageEnd=null, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=CROOK A A, POWERS R, journalName=Molecules, refType=null, unstructuredReference=CROOK A A, POWERS R. Quantitative NMR-based biomedical metabolomics: current status and applications[J]. Molecules, 2020; 25(21):5128. DOI: 10.3390/molecules25215128, articleTitle=Quantitative NMR-based biomedical metabolomics: current status and applications, refAbstract=null), Reference(id=1193928895096390337, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2017, volume=80, issue=2, pageStart=415, pageEnd=426, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=DUDEK M K, GLIŃSKI V B, DAVEY M H, journalName=J Nat Prod, refType=null, unstructuredReference=DUDEK M K, GLIŃSKI V B, DAVEY M H, et al. Trimeric and tetrameric a-type procyanidins from peanut skins[J]. J Nat Prod, 2017, 80(2): 415-426., articleTitle=Trimeric and tetrameric a-type procyanidins from peanut skins, refAbstract=null), Reference(id=1193928895163499202, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2015, volume=63, issue=12, pageStart=3135, pageEnd=3143, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=EIFF J, MONAKHOVA Y B, DIEHL B W K, journalName=J Agric Food Chem, refType=null, unstructuredReference=EIFF J, MONAKHOVA Y B, DIEHL B W K. Multicomponent analysis of fat-and water-soluble vitamins and auxiliary substances in multivitamin preparations by qNMR[J]. J Agric Food Chem, 2015, 63(12): 3135-3143., articleTitle=Multicomponent analysis of fat-and water-soluble vitamins and auxiliary substances in multivitamin preparations by qNMR, refAbstract=null), Reference(id=1193928896199492291, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2011, volume=83, issue=22, pageStart=8766, pageEnd=8771, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=DO N M, OLIVIER M A, SALISBURY J J, journalName=Anal Chem, refType=null, unstructuredReference=DO N M, OLIVIER M A, SALISBURY J J, et al. Application of quantitative 19F and 1H-NMR for reaction monitoring and in situ yield determinations for an early stage pharmaceutical candidate[J]. Anal Chem, 2011, 83(22): 8766-8771., articleTitle=Application of quantitative 19F and 1H-NMR for reaction monitoring and in situ yield determinations for an early stage pharmaceutical candidate, refAbstract=null), Reference(id=1193928896274989764, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2023, volume=45, issue=6, pageStart=123, pageEnd=130, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=HUANG T, WANG J Y, ZHANG W, journalName=Chem Reagents(化学试剂), refType=null, unstructuredReference=HUANG T, WANG J Y, ZHANG W, et al. Research progress in the application of quantitative nuclear magnetic resonance method in recent decade[J]. Chem Reagents(化学试剂), 2023, 45(6): 123-130., articleTitle=Research progress in the application of quantitative nuclear magnetic resonance method in recent decade, refAbstract=null), Reference(id=1193928896333710021, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2012, volume=75, issue=4, pageStart=834, pageEnd=851, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=PAULI G F, GÖDECKE T, JAKI B U, journalName=J Nat Prod, refType=null, unstructuredReference=PAULI G F, GÖDECKE T, JAKI B U, et al. Quantitative 1HNMR. Development and potential of an analytical method: An update[J]. J Nat Prod, 2012, 75(4): 834-851., articleTitle=Quantitative 1HNMR. Development and potential of an analytical method: An update, refAbstract=null), Reference(id=1193928896392430278, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=629, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=null, journalName=USP 40-NF 30, refType=null, unstructuredReference=USP 40-NF 30[S]. 2020: 629., articleTitle=null, refAbstract=null), Reference(id=1193928896451150535, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2016, volume=null, issue=null, pageStart=47, pageEnd=null, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=null, journalName=JP 17, refType=null, unstructuredReference=JP 17[S]. 2016: 47., articleTitle=null, refAbstract=null), Reference(id=1193928896514065096, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=58, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=null, journalName=EP 10.0, refType=null, unstructuredReference=EP 10.0[S]. 2020: 58., articleTitle=null, refAbstract=null), Reference(id=1193928896593756873, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2020, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=null, journalName=Ch.P (2020) Vol Ⅳ (中国药典2020年版.四部), refType=null, unstructuredReference=Ch.P (2020) Vol Ⅳ (中国药典2020年版.四部) [S]. 2020: 53., articleTitle=null, refAbstract=null), Reference(id=1193928896656671434, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2020, volume=40, issue=11, pageStart=1923, pageEnd=1927, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=LIU Y, ZHANG C Y, LUAN L, journalName=Chin J Pharm Anal (药物分析杂志), refType=null, unstructuredReference=LIU Y, ZHANG C Y, LUAN L, et al. Common concerns in application of proton qNMR in characterizing the assay of chemical reference substances[J]. Chin J Pharm Anal (药物分析杂志), 2020, 40(11): 1923-1927., articleTitle=Common concerns in application of proton qNMR in characterizing the assay of chemical reference substances, refAbstract=null), Reference(id=1193928896723780299, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2020, volume=68, issue=9, pageStart=868, pageEnd=878, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=MIURA T, SUGIMOTO N, BHAVARAJU S, journalName=Chem Pharm Bull (Tokyo), refType=null, unstructuredReference=MIURA T, SUGIMOTO N, BHAVARAJU S, et al. Collaborative study to validate purity determination by 1H quantitative NMR spectroscopy by using internal calibration methodology[J]. Chem Pharm Bull (Tokyo), 2020, 68(9): 868-878., articleTitle=Collaborative study to validate purity determination by 1H quantitative NMR spectroscopy by using internal calibration methodology, refAbstract=null), Reference(id=1193928896786694860, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2012, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=YANG X, journalName=Application of NMR in quantification of chemical reference, refType=null, unstructuredReference=YANG X. Application of NMR in quantification of chemical reference[D]. Beijing: National Institutes For Food and Drug Control, 2012., articleTitle=null, refAbstract=null), Reference(id=1193928896862192333, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2014, volume=93, issue=null, pageStart=102, pageEnd=110, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=WEBER M, HELLRIEGEL C, RUECK A, journalName=J Pharm Biomed Anal, refType=null, unstructuredReference=WEBER M, HELLRIEGEL C, RUECK A, et al. Using high-performance 1H-NMR (HP-qNMR®) for the certification of organic reference materials under accreditation guidelines-describing the overall process with focus on homogeneity and stability assessment[J]. J Pharm Biomed Anal, 2014, 93: 102-110., articleTitle=Using high-performance 1H-NMR (HP-qNMR®) for the certification of organic reference materials under accreditation guidelines-describing the overall process with focus on homogeneity and stability assessment, refAbstract=null), Reference(id=1193928896920912590, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2010, volume=52, issue=5, pageStart=645, pageEnd=651, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=RUNDLÖF T, MATHIASSON M, BEKIROGLU S, journalName=J Pharm Biomed Anal, refType=null, unstructuredReference=RUNDLÖF T, MATHIASSON M, BEKIROGLU S, et al. Survey and qualification of internal standards for quantification by 1H-NMR spectroscopy[J]. J Pharm Biomed Anal, 2010, 52(5): 645-651., articleTitle=Survey and qualification of internal standards for quantification by 1H-NMR spectroscopy, refAbstract=null), Reference(id=1193928896979632847, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2005, volume=38, issue=5, pageStart=813, pageEnd=823, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=MALZ F, JANCKE H, journalName=J Pharm Biomed Anal, refType=null, unstructuredReference=MALZ F, JANCKE H. Validation of quantitative NMR[J]. J Pharm Biomed Anal, 2005, 38(5): 813-823., articleTitle=Validation of quantitative NMR, refAbstract=null), Reference(id=1193928897046741712, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, doi=null, pmid=null, pmcid=null, year=2012, volume=35, issue=null, pageStart=5, pageEnd=26, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=BHARTI S K, ROY R, journalName=TrAC Trends Anal Chem, refType=null, unstructuredReference=BHARTI S K, ROY R. Quantitative 1H-NMR spectroscopy[J]. TrAC Trends Anal Chem, 2012, 35: 5-26., articleTitle=Quantitative 1H-NMR spectroscopy, refAbstract=null)], funds=[Fund(id=1193928894320444088, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, awardId=2023Y002, language=CN, fundingSource=国家药典委员会药品标准制修订研究课题资助(2023Y002), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1193928892202320537, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, xref=null, ext=[AuthorCompanyExt(id=1193928892210709146, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, companyId=1193928892202320537, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Green Pharmaceutical Collaborative Innovation Center, Zhejiang University of Technology, Hangzhou 310014, China), AuthorCompanyExt(id=1193928892214903451, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, companyId=1193928892202320537, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=浙江工业大学绿色制药协同创新中心, 杭州 310014)])], figs=[ArticleFig(id=1193928893372531374, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, label=Fig.1, caption=Structural formula of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), figureFileSmall=TORok64htjwkPrN9nir1pQ==, figureFileBig=1QjnmI68iA65Rh8Bz2tB/g==, tableContent=null), ArticleFig(id=1193928893502554799, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, label=图1, caption=二油酰基磷脂酰胆碱(DOPC)的结构式, figureFileSmall=TORok64htjwkPrN9nir1pQ==, figureFileBig=1QjnmI68iA65Rh8Bz2tB/g==, tableContent=null), ArticleFig(id=1193928893636772528, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, label=Fig.2, caption=1H-NMR spectrum of 1,3,5-trimethoxybenzene(A), DOPC(B) and the mixture of 1,3,5-trimethoxybenzene and DOPC(C), figureFileSmall=S38gnShHYwi9QC2XIZdVAw==, figureFileBig=aY2QW0KTqszlo7Rk+JCABA==, tableContent=null), ArticleFig(id=1193928893729047217, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, label=图2, caption=1,3,5-三甲氧基苯(A)、DOPC(B)及1,3,5-三甲氧基苯和DOPC混合物(C)的1H-NMR谱图, figureFileSmall=S38gnShHYwi9QC2XIZdVAw==, figureFileBig=aY2QW0KTqszlo7Rk+JCABA==, tableContent=null), ArticleFig(id=1193928893817127602, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, label=Tab.1, caption=

Results for linear relation testing of DOPC

, figureFileSmall=null, figureFileBig=null, tableContent=
ρ(DOPC)/mg·mL-1 mS/mR AS/AR
1.6 0.41 0.178
3.0 0.75 0.319
4.0 1.00 0.457
5.33 1.33 0.535
10 2.84 1.250
20 5.09 2.150
25 6.28 2.679
), ArticleFig(id=1193928893892625075, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, label=表1, caption=

二油酰基磷脂酰胆碱(DOPC)线性实验结果

, figureFileSmall=null, figureFileBig=null, tableContent=
ρ(DOPC)/mg·mL-1 mS/mR AS/AR
1.6 0.41 0.178
3.0 0.75 0.319
4.0 1.00 0.457
5.33 1.33 0.535
10 2.84 1.250
20 5.09 2.150
25 6.28 2.679
), ArticleFig(id=1193928893951345332, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, label=Tab.2, caption=

Comparison of the results for determining the content of DOPC samples by qHNMR and molybdenum blue spectrophotometry

, figureFileSmall=null, figureFileBig=null, tableContent=
Sample
No.		 Content
(qHNMR)/%		 Content(molybdenum blue
spectrophotometric method)/%
S1 97.28 98.68
S2 98.74 100.45
S3 98.70 97.15
S4 96.98 97.59
S5 96.82 99.51
S6 96.72 98.46
S7 97.67 96.71
S8 96.83 96.07
), ArticleFig(id=1193928894018454197, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, label=表2, caption=

qHNMR与钼蓝分光光度法测定DOPC样品含量的结果比较

, figureFileSmall=null, figureFileBig=null, tableContent=
Sample
No.		 Content
(qHNMR)/%		 Content(molybdenum blue
spectrophotometric method)/%
S1 97.28 98.68
S2 98.74 100.45
S3 98.70 97.15
S4 96.98 97.59
S5 96.82 99.51
S6 96.72 98.46
S7 97.67 96.71
S8 96.83 96.07
), ArticleFig(id=1193928894081368758, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=EN, label=Tab.3, caption=

1H-NMR data of DOPC(CDCl3)

, figureFileSmall=null, figureFileBig=null, tableContent=
Conformation Peak
shape		 Attribution
δ Number of protons
5.40-5.27 4H m H14,H15,H33,H34
5.19 1H m H3
4.43-4.26 3H m H5,H2
4.12 1H dd H2
3.94 2H m H49
3.83-3.76 2H m H50
3.36 10H s H52,H53,H54
2.28 4H q H7,H26
2.00 8H q H13,H16,H32,H35
1.58 4H m H8,H27
1.29 39H t -CH2-
0.87 6H t H23,H42
), ArticleFig(id=1193928894156866231, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1193877805848035790, language=CN, label=表3, caption=

DOPC样品的1H-NMR测定结果(CDCl3)

, figureFileSmall=null, figureFileBig=null, tableContent=
Conformation Peak
shape		 Attribution
δ Number of protons
5.40-5.27 4H m H14,H15,H33,H34
5.19 1H m H3
4.43-4.26 3H m H5,H2
4.12 1H dd H2
3.94 2H m H49
3.83-3.76 2H m H50
3.36 10H s H52,H53,H54
2.28 4H q H7,H26
2.00 8H q H13,H16,H32,H35
1.58 4H m H8,H27
1.29 39H t -CH2-
0.87 6H t H23,H42
)], attaches=null, journal=Journal(id=1190317596361715715, delFlag=0, nameCn=中国药学杂志, nameEn=Chinese Pharmaceutical Journal, nameHistory1=null, nameHistory2=null, issn=1001-2494, eissn=null, cn=11-2162/R, coden=null, periodic=3, language=CN, oaType=null, 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=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=hRN1R6HnoNwYkve/JRn0DA==, journalPrice=null, startedYear=null, abbrevIsoEn=null, journalRemark=null, publicationField=null, createdTime=1761723430007, updatedTime=1761735858241, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=C, firstLetterEn=C, subjectCode=Life Sciences, subjectName=Life Sciences, subjectCodeEn=Life Sciences, subjectNameEn=null, picCn=hRN1R6HnoNwYkve/JRn0DA==, picEn=xSRntM4yOh2wVIE2w+OjYg==, jcr=null, cjcr=null, exts=[JournalExt(id=1190369724262355196, language=CN, name=中国药学杂志, 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=1761735858264, updatedTime=1761735858264, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://zgyxzzauthor.manuscriptcloud.com/login, submissionEditorUrl=https://zgyxzzeditor.manuscriptcloud.com/login, submissionReviewUrl=https://zgyxzzauthor.manuscriptcloud.com/login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1190369724358824189, language=EN, name=Chinese Pharmaceutical Journal, 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=1761735858287, updatedTime=1761735858287, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://zgyxzzauthor.manuscriptcloud.com/login, submissionEditorUrl=https://zgyxzzeditor.manuscriptcloud.com/login, submissionReviewUrl=https://zgyxzzauthor.manuscriptcloud.com/login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1190317699101192196, websiteList=[Website(id=1190317834875011552, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1190317699101192196, 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/zgyxzz/CN, language=CN, createTime=1761723486870, createBy=18614031015, updateTime=1761723510130, updateBy=18614031015, name=中国药学杂志-中文, tplId=1146099689490845704, title=中国药学杂志, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1190318144041353703, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=articleTextType, value=kx, createTime=1761723560581, updateTime=1761723560581, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144016187876, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=banner, value=null, createTime=1761723560575, updateTime=1761723560575, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144062325226, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=grayFlag, value=0, createTime=1761723560586, updateTime=1761723560586, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144007799267, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=logo, value=https://castjournals.cast.org.cn/joweb/zgyxzz/CN/file/pic?fileId=puyAm9wIHqZks7K8hj8APQ==, createTime=1761723560573, updateTime=1761723560573, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144074908140, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=minRunFlag, value=0, createTime=1761723560589, updateTime=1761723560589, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144032965094, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zgyxzz/CN/file/pic, createTime=1761723560579, updateTime=1761723560579, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144070713835, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=silenceFlag, value=0, createTime=1761723560588, updateTime=1761723560588, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144024576485, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1761723560577, updateTime=1761723560577, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144049742312, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=themeColor, value=null, createTime=1761723560583, updateTime=1761723560583, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318144053936617, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834875011552, code=themeStyle, value=null, createTime=1761723560584, updateTime=1761723560584, creator=18614031015, updator=18614031015)]), Website(id=1190317834937926113, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1190317699101192196, 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/zgyxzz/EN, language=EN, createTime=1761723486885, createBy=18614031015, updateTime=1761723527689, updateBy=18614031015, name=中国药学杂志-英文, tplId=1146101810881728533, title=Chinese Pharmaceutical Journal, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1190318170478051825, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=articleTextType, value=kx, createTime=1761723566884, updateTime=1761723566884, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170461274606, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=banner, value=null, createTime=1761723566880, updateTime=1761723566880, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170494829044, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=grayFlag, value=0, createTime=1761723566888, updateTime=1761723566888, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170452885997, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=logo, value=https://castjournals.cast.org.cn/joweb/zgyxzz/EN/file/pic?fileId=puyAm9wIHqZks7K8hj8APQ==, createTime=1761723566878, updateTime=1761723566878, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170507411958, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=minRunFlag, value=0, createTime=1761723566891, updateTime=1761723566891, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170473857520, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zgyxzz/EN/file/pic, createTime=1761723566883, updateTime=1761723566883, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170503217653, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=silenceFlag, value=0, createTime=1761723566890, updateTime=1761723566890, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170465468911, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1761723566881, updateTime=1761723566881, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170482246130, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=themeColor, value=null, createTime=1761723566885, updateTime=1761723566885, creator=18614031015, updator=18614031015), WebsiteProps(id=1190318170486440435, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1190317834937926113, code=themeStyle, value=null, createTime=1761723566886, updateTime=1761723566886, creator=18614031015, updator=18614031015)])], journalTitle=中国药学杂志, weixinUrl=null, journalUrl=http://www.zgyxzz.com.cn/, iacademicId=null, status=1, seqNo=null, journalTitleEn=Chinese Pharmaceutical Journal, journalPhotoCn=hRN1R6HnoNwYkve/JRn0DA==, journalPhotoEn=xSRntM4yOh2wVIE2w+OjYg==, 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/zgyxzz/CN/10.11669/cpj.2025.02.011, detailUrlEn=https://castjournals.cast.org.cn/joweb/zgyxzz/EN/10.11669/cpj.2025.02.011, pdfUrlCn=https://castjournals.cast.org.cn/joweb/zgyxzz/CN/PDF/10.11669/cpj.2025.02.011, pdfUrlEn=https://castjournals.cast.org.cn/joweb/zgyxzz/EN/PDF/10.11669/cpj.2025.02.011, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, reference=null)
收藏切换
定量核磁共振氢谱法测定药用辅料二油酰基磷脂酰胆碱的含量
收藏切换
PDF下载
王娅雯 , 陈雪帆 *
中国药学杂志 | 论著 2025,60(2): 184-188
收起
收藏切换
中国药学杂志 | 论著 2025, 60(2): 184-188
定量核磁共振氢谱法测定药用辅料二油酰基磷脂酰胆碱的含量
全屏
王娅雯, 陈雪帆*
作者信息
  • 浙江工业大学绿色制药协同创新中心, 杭州 310014

    • 王娅雯,女,硕士研究生 研究方向:药物分析

通讯作者:

*陈雪帆,男,硕士,高级工程师 研究方向:药物分析 Tel:(0517)88871559
Quantitative Analysis of 1,2-Dioleoyl-sn-glycero-3-Phosphocholine in Pharmaceutical Excipients by Proton Nuclear Magnetic Resonance
Yawen WANG, Xuefan CHEN*
Affiliations
  • Green Pharmaceutical Collaborative Innovation Center, Zhejiang University of Technology, Hangzhou 310014, China
出版时间: 2025-01-22 doi: 10.11669/cpj.2025.02.011
文章导航
收藏切换
摘要
收起

目的 建立测定二油酰基磷脂酰胆碱(1,2-dioleoyl-SN-glycero-3-phosphocholine,DOPC)含量的定量核磁共振氢谱法(quantitative proton nuclear magnetic resonance, qHNMR)。方法 采用Bruker AVANCE Ⅱ 600 MHz核磁共振波谱仪,采集DOPC的核磁共振氢谱,以1,3,5-三甲氧基苯为内标物,氘代氯仿为溶剂,30°脉冲,扫描次数为16次,测试温度25 ℃,采集时间(AQ)为5 s,弛豫延迟时间(D1)为35 s,对DOPC进行定量分析。结果 样品的1H-NMR谱在化学位移δ 0.87出现甲基的质子信号,DOPC和内标物定量峰信号在1H-NMR谱上分离度良好,DOPC在线性范围内线性关系良好(r>0.999 6),方法精密度和重复性良好,DOPC含量为96.7%~98.7%,测定结果与磷钼酸比色法测定结果基本一致。结论 建立的qHNMR方法可以对DOPC进行准确定量,相比于经典的磷钼酸比色方法更加快速,并且不需要复杂的前处理操作。

定量核磁共振氢谱法  /  药用辅料  /  含量测定  /  内标法  /  二油酰基磷脂酰胆碱

OBJECTIVE To develop a quantitative proton nuclear magnetic resonance (qHNMR) method for the determination of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). METHODS A Bruker AVANCE Ⅱ 600 MHz NMR resonance spectra was utilized to acquire the NMR spectra of DOPC. The compound 1,3,5-trimethoxybenzene served as the internal standard, deuterated chloroform as the solvent, with 30° pulses, 16 scans, a test temperature of 25 ℃, and an acquisition time (AQ) of 5 s. The relaxation delay time (D1) was set at 35 s for quantitative analysis of DOPC. RESULTS The sample's 1H-NMR spectra displayed a methyl proton signal at chemical shift δ 0.87; the quantitative peak signals of DOPC and internal standard were well resolved on the 1H-NMR spectra with good linear relationship for DOPC (r>0.9996). The method demonstrated accuracy and repeatability with DOPC content ranging from 96.7% to 98.7%, consistent with results obtained from phosphomolybdic acid colorimetry. CONCLUSION The established qHNMR method accurately quantifies DOPC, is faster than the classical phosphomolybdate colometry method, requires no complex pretreatment operations.

quantitative nuclear magnetic resonance  /  pharmaceutical excipient  /  content determination  /  internal standard method  /  DOPC
王娅雯, 陈雪帆. 定量核磁共振氢谱法测定药用辅料二油酰基磷脂酰胆碱的含量. 中国药学杂志, 2025 , 60 (2) : 184 -188 . DOI: 10.11669/cpj.2025.02.011
Yawen WANG, Xuefan CHEN. Quantitative Analysis of 1,2-Dioleoyl-sn-glycero-3-Phosphocholine in Pharmaceutical Excipients by Proton Nuclear Magnetic Resonance[J]. Chinese Pharmaceutical Journal, 2025 , 60 (2) : 184 -188 . DOI: 10.11669/cpj.2025.02.011
正文
收起
广义上卵磷脂是由多种成分(磷脂酰胆碱、磷脂酰丝氨酸和磷脂酰乙醇胺等)组成的混合磷脂[1],天然卵磷脂来源广泛,大量存在于动植物体内,最有实用价值的卵磷脂原料是大豆和蛋黄[2]。然而,从天然原料中提取的大豆磷脂和蛋黄磷脂成分繁杂、稳定性差,增加了应用过程中的不确定性因素,且不利于质量控制。因此,在药物研究中,具有单一组分的高纯度卵磷脂则更受青睐,由于天然卵磷脂的纯化工艺复杂繁琐,研究人员便将重点放在了化学合成上,通过人工合成获得具有明确结构的单一组分,从而得到具有一定特性的磷脂。二油酰基磷脂酰胆碱(1,2-dioleoyl-sn-glycero-3-phosphocholine,DOPC)是一种常用的合成卵磷脂[3],具有两性分子结构(图1),这种独特的理化性质和生理活性使其在医药领域具有十分重要的意义,主要作为药用辅料用于注射液、混悬液、乳剂等多种不同剂型的药物中[4-5]或直接作为有效成分使用;因与人体具有较高的相容性且稳定性好纯度高,适合作为膜材用于脂质体的制备,如Skyepharma公司将无菌的阿糖胞苷悬浮液包装到由胆固醇、甘油三油酸酯以及二油酸磷脂酰胆碱、二棕榈酰磷脂酰甘油制备而成的多室脂质体中[6];DOPC的疏水端由不饱和的油酸组成,广泛作为抗氧剂应用于食品行业[7]。DOPC作为重要的药用辅料,确保其安全有效、质量可控对于人类健康事业的发展至关重要。
核磁共振波谱(NMR)法可以在物质的分析研究中提供精确的定性和定量信息,因其独特的分析能力,目前已成为了一种研究物质结构和特性的新兴技术。由于核磁共振活性核的普遍存在,NMR法在代谢组学[8]、结构鉴定[9]、含量测定[10]和反应监测[11]等方面具有极其广泛的应用。定量核磁共振氢谱法(qHNMR)作为一种用于有机化合物定值的潜在基准方法,具有许多优点[12-13]:NMR法通过记录静磁场中磁性原子核与电磁波相互作用的结果来分析样品,不会破坏样品结构和化学特性;不需要提供待测样品的对照品即可进行定量分析,并且具有高度的选择性;对样品的要求低,不需要复杂的前处理工作,仪器操作简单分析速度快。各国药典均已收载该方法[14-17],并广泛应用于药物的质量分析研究。常规的测定磷脂酰胆碱含量的方法是高效液相色谱 (HPLC) 法,DOPC不含有生色基团,无法使用常规的紫外(UV)检测器进行含量测定,通常选择蒸发光散射(ELSD)检测器进行检测。ELSD的原理是将流动相雾化形成小液滴,然后加热蒸发,不易挥发的化合物形成微小颗粒,通过散射光信号来检测和定量目标化合物。因此,ELSD检测器要求流动相及流动相中加入的修饰剂必须具有良好的挥发性,这样就使非挥发性的缓冲盐的应用受到了限制;液相的平衡时间长,且ELSD检测器的灵敏度会低于UV检测器,样品中的溶剂残留也可能导致散射光强度的非线性响应。DOPC的分子式为C44H84NO8P,含有磷,因此可通过比较测定样品中磷元素的含量来折算DOPC的含量。但该方法专属性较差,且实验过程繁杂,影响定量结果准确性的因素较多。结合qHNMR的仪器性能和方法优势,本研究首次采用NMR法对DOPC进行含量测定,为DOPC及其他合成磷脂的质量研究提供技术支持。
本实验收集了来自4个厂家共8批次的DOPC药用辅料,采用qHNMR技术,测定其DOPC的含量,对专属性、精密度、重复性、线性范围等进行方法学考察,实验结果表明,该方法可准确快速地对DOPC定量分析。
1 仪器与试药
收起
Bruker AVANCE Ⅱ 600 MHz型核磁共振波谱仪(Bruker公司);Mettler Toledo 电子天平(精度0.001 mg,上海梅特勒-托利多有限公司); Milli-Q超纯水仪(Millipore 公司)。
氘代氯仿(CDCl3,Cambridge Isotope Laboratories公司,批号: PR-31594/04300 CL1,含量99.8%);1,3,5-三甲氧基苯(上海皓鸿生物医药科技有限公司,批号:Lf0520134937,含量97.37%);去离子水(Mill-Q 制备)。
DOPC:市售样品来自4个不同厂家共8批样品,编号分别为S1~S8。
2 实验方法
收起
2.1 溶液的配制
2.1.1 1,3,5-三甲氧基苯内标溶液
精密称取1,3,5-三甲氧基苯约80 mg置于5 mL量瓶内,用CDCl3定容得到内标溶液。
2.1.2 核磁共振供试品溶液配制
取8批DOPC样品约20 mg,精密称定,加入内标溶液500 μL,振荡使其完全溶解,转移至5 mm核磁管待测。
2.2 核磁测试参数设置
qHNMR采用30°脉冲,谱宽(SW)设置为20.025 4,中心频率为6.175,采样次数(NS)为16次,测试温度为25 ℃,采样时间(AQ)为5 s,弛豫延迟时间(D1)为35 s,采样点数6.5×104。在上述实验条件下,调整仪器参数、调谐、锁场、匀场、采样。
2.3 核磁数据处理计算
将采集得到的数据使用MestReNova 12软件进行傅里叶变换,设置溶剂峰,进行相位矫正和基线矫正,选定内标和样品定量特征峰,积分5次取平均值[18],按公式1计算结果。
Px= I x I s t d N s t d N x M x M s t d W s t d W x×Pstd
式中,Ix和Istd分别为待测样品与内标物定量峰的平均积分面积;Nx和Nstd分别为待测样品与内标物定量峰积分信号所包含的质子数;Mx和Mstd分别为待测样品与内标物的相对分子质量;Wx和Wstd分别为待测样品与内标物的质量;Px和Pstd分别为待测样品和内标物的质量百分含量。
2.4 分析方法学考察
2.4.1 线性关系考察
精密称取内标物40 mg置于10 mL量瓶中用氘代氯仿定容,得到质量浓度为4 mg·mL-1的内标溶液。分别称取25、20、10、5.33、4.0、3.0和1.6 mg样品,各加入1 mL上述内标溶液,得到样品质量浓度范围为1.6~25 mg·mL-1的待测溶液。以样品与内标物的取样质量比值(mS/mR)为横坐标,两者定量峰积分面积比值(AS/AR)的平均值为纵坐标进行线性回归,回归方程为:y=0.425 3x+0.005,r=0.999 6表明样品与内标物质量比值在0. 41~6.28内与两者定量峰积分面积比值呈良好的线性关系(表1)。
2.4.2 精密度试验
取“2.1.2”项下同一份供试品溶液,按“2.2”项下条件连续测定6次,计算AS/AR的比值,相对标准偏差(RSD)为1.3%。
2.4.3 稳定性试验
取同一份供试品溶液,在室温下放置0、6、18、24、36、48 h分别进行测定,计算AS/AR的比值,RSD为0.80%,表明供试品溶液室温放置48 h内稳定。
2.4.4 重复性试验
按“2.1.2”项下条件平行配制6份供试品溶液,按“2.2”项下实验条件测定,计算AS/AR的比值,RSD为1.16%,重复性良好。
2.4.5 专属性考察
DOPC样品、1,3,5-三甲氧基苯内标物和两者混合溶液的核磁共振氢谱见图2,分别选择样品位于0.87和内标位于6.08的两处信号作为两个化合物的定量峰。二者互不干扰且基线平整,专属性良好。
2.5 样品测定
取4个厂家共8批样品按“2.1.2”项下方法配制供试品溶液S1~S8,按“2.2”项下方法进行测定。采用qHNMR法和磷钼酸比色法测定DOPC样品含量的结果见表2,对qHNMR法和磷钼酸比色法结果进行配对t检验,P>0.05(P=0.297),结果表明,两种方法测得结果基本一致。
3 结果与讨论
收起
3.1 DOPC的氢谱解析
采集DOPC的氢谱,对其质子信号进行解析归属,结果见表3。
3.2 内标物的选择
在核磁共振谱中,信号峰面积与它所代表的核的数量成正比,分子中每个氢核的共振频率会根据化学环境的不同而发生偏移。因此可以向样品中添加适量可计量溯源的替代物质作为qNMR的内部标准[19]。再通过公式1来确定样品的含量。在进行qHNMR实验时,应尽量选择纯度高易称量、化学惰性即不与样品或溶剂发生反应,且在溶剂中溶解完全的物质。根据上述原则,本实验选取了1,3,5-三甲氧基苯环上的质子峰作为内标物定量信号,样品的定量峰为化学位移δ 0.87的甲基信号峰,二者完全分离且基线平整,不受其他信号峰的干扰。
3.3 定量峰的选择
一般选择与相邻信号分离度良好的信号峰作为样品的定量峰。在本实验中,分别统计了样品和内标物不同信号作为定量峰时样品的浓度。结果表明,样品选择化学位移为δ 0.87的甲基信号峰、内标选择δ 6.09的质子信号峰与其他信号峰分离度良好,定量的结果与真实值更接近。
3.4 氘代试剂的选择
分析物和内标应在氘代试剂内完全溶解,不能有悬浮或析出,否则将导致定量结果的不准确[20]。常用溶剂包括重水、氘代丙酮、氘代三氯甲烷、氘代甲醇以及氘代二甲亚砜等。DOPC易溶于三氯甲烷,可溶于甲醇和乙醇,不溶于丙酮和水。内标物不溶于水,在三氯甲烷中极易溶解。因此,选择氘代氯仿作为溶剂。
3.5 仪器参数的选择
仪器的参数设置直接影响实验结果的准确性[21]。影响准确性的参数主要包括弛豫延迟时间D1、扫描次数(NS)、激发脉冲的角度(P1)和采集时间等。D1是影响质子信号峰面积准确性的重要参数,D1的设定与纵向弛豫时间(T1)直接相关。有研究表明,若P1为30°,D1应满足大于7/3T1[22];若P1为90°,D1应满足大于5T1[23],测定的结果可以得到保障。采用反转恢复法(inversion-recovery)测得DOPC和内标物定量峰的T1值分别为2.528 s和3.664 s,为了使核自旋沿着极化磁场的方向完全恢复平衡,保证被积分的信号强度与原子核数目完全成正比,本次实验设定D1为35 s。qHNMR的信噪比一般要求不小于250[24],扫描次数与信噪比成正比,但扫描次数的增加会延长实验时间。本实验分别考察了NS为4、8、16、24和32次对定量结果的影响,S/N均满足上述要求,定量结果的RSD为0.43%,无明显差异。本实验选择扫描次数为16可以满足实验精度和准确度要求。
3.6 qHNMR在药品方面的应用和优势
随着超导技术、低温探头和脉冲傅里叶变换等先进技术的不断发展,qHNMR的灵敏度和准确度显著提高,已经成为复杂样品结构分析的标准工具。相比于气相色谱法和液相色谱法,qHNMR不破坏样品,能够同时进行准确的定性和定量分析,试验结束可以回收样品,提高样品利用率。
基金
收起
  • 国家药典委员会药品标准制修订研究课题资助(2023Y002)
文献
收起
参考文献 引证文献
排序方式：
[1]
DRESCHER S, VAN HOOGEVEST P. The phospholipid research center: current research in phospholipids and their use in drug delivery[J]. Pharmaceutics, 2020, 12(12): 1235. DOI: 10.3390/pharmaceutics12121235.
[2]
ZHANG Y Y. Study on the purification method of phosphatidylcholine with high content[D]. Hangzhou: Zhejiang University, 2005.
[3]
Suzhou South East Pharmaceuticals Co.,Ltd, Jiangsu Southeast Nano Materials Co.,Ltd. The invention discloses a preparation method for dioleoyl phosphatidylcholine: China, 201911092006. 5[P]. 2020-07-28.
[4]
FRICKER G, KROMP T, WENDEL A, et al. Phospholipids and lipid-based formulations in oral drug delivery[J]. Pharm Res, 2010, 27(8): 1469-1486.
[5]
YANG R, ZHANG X, LI F, et al. Role of phospholipids and copolymers in enhancing stability and controlling degradation of intravenous lipid emulsions[J]. Colloids Surf A, 2013, 436: 434-442.
[6]
MANTRIPRAGADA S. A lipid based depot ( DepoFoam® technology) for sustained release drug delivery[J]. Prog Lipid Res, 2002, 41 (5): 392-406.
[7]
KIM H, WOO Y, CHOI H, et al. Dioleylphosphatidylcholine increases the antioxidant properties of ascorbyl palmitate in bulk oils compared to other hydrophilic and lipophilic antioxidants[J]. Food Chem, 2021, 349: 129082. DOI: 10.1016/j.foodchem.2021.129082
[8]
CROOK A A, POWERS R. Quantitative NMR-based biomedical metabolomics: current status and applications[J]. Molecules, 2020; 25(21):5128. DOI: 10.3390/molecules25215128
[9]
DUDEK M K, GLIŃSKI V B, DAVEY M H, et al. Trimeric and tetrameric a-type procyanidins from peanut skins[J]. J Nat Prod, 2017, 80(2): 415-426.
[10]
EIFF J, MONAKHOVA Y B, DIEHL B W K. Multicomponent analysis of fat-and water-soluble vitamins and auxiliary substances in multivitamin preparations by qNMR[J]. J Agric Food Chem, 2015, 63(12): 3135-3143.
[11]
DO N M, OLIVIER M A, SALISBURY J J, et al. Application of quantitative 19F and 1H-NMR for reaction monitoring and in situ yield determinations for an early stage pharmaceutical candidate[J]. Anal Chem, 2011, 83(22): 8766-8771.
[12]
HUANG T, WANG J Y, ZHANG W, et al. Research progress in the application of quantitative nuclear magnetic resonance method in recent decade[J]. Chem Reagents(化学试剂), 2023, 45(6): 123-130.
[13]
PAULI G F, GÖDECKE T, JAKI B U, et al. Quantitative 1HNMR. Development and potential of an analytical method: An update[J]. J Nat Prod, 2012, 75(4): 834-851.
[14]
USP 40-NF 30[S]. 2020: 629.
[15]
JP 17[S]. 2016: 47.
[16]
EP 10.0[S]. 2020: 58.
[17]
Ch.P (2020) Vol Ⅳ (中国药典2020年版.四部) [S]. 2020: 53.
[18]
LIU Y, ZHANG C Y, LUAN L, et al. Common concerns in application of proton qNMR in characterizing the assay of chemical reference substances[J]. Chin J Pharm Anal (药物分析杂志), 2020, 40(11): 1923-1927.
[19]
MIURA T, SUGIMOTO N, BHAVARAJU S, et al. Collaborative study to validate purity determination by 1H quantitative NMR spectroscopy by using internal calibration methodology[J]. Chem Pharm Bull (Tokyo), 2020, 68(9): 868-878.
[20]
YANG X. Application of NMR in quantification of chemical reference[D]. Beijing: National Institutes For Food and Drug Control, 2012.
[21]
WEBER M, HELLRIEGEL C, RUECK A, et al. Using high-performance 1H-NMR (HP-qNMR®) for the certification of organic reference materials under accreditation guidelines-describing the overall process with focus on homogeneity and stability assessment[J]. J Pharm Biomed Anal, 2014, 93: 102-110.
[22]
RUNDLÖF T, MATHIASSON M, BEKIROGLU S, et al. Survey and qualification of internal standards for quantification by 1H-NMR spectroscopy[J]. J Pharm Biomed Anal, 2010, 52(5): 645-651.
[23]
MALZ F, JANCKE H. Validation of quantitative NMR[J]. J Pharm Biomed Anal, 2005, 38(5): 813-823.
[24]
BHARTI S K, ROY R. Quantitative 1H-NMR spectroscopy[J]. TrAC Trends Anal Chem, 2012, 35: 5-26.
2025年第60卷第2期
PDF下载
131
55
引用本文
BibTeX
文章信息
doi: 10.11669/cpj.2025.02.011
  • 接收时间：2024-05-29
  • 首发时间：2025-11-08
  • 出版时间：2025-01-22
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2024-05-29
基金
国家药典委员会药品标准制修订研究课题资助(2023Y002)
作者信息
    浙江工业大学绿色制药协同创新中心, 杭州 310014

通讯作者:

*陈雪帆,男,硕士,高级工程师 研究方向:药物分析 Tel:(0517)88871559
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/zgyxzz/CN/10.11669/cpj.2025.02.011
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