人体生物等效性试验中生物样品分析的关键问题研究
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摘要
采用体内生物等效性试验的方法开展一致性评价是仿制药申请的基础,生物等效性试验首选药动学研究的方法,而药动学中生物样品分析是最为重要的环节,它将直接影响药品的安全性和有效性,为生物等效性试验的结果做出关键性决定。目前我国的生物样品分析质量还有很大提升空间,基于此,本文根据相关指导原则,结合工作实际,针对生物等效性试验中生物样品分析方法的建立、验证、测试、记录和注意事项等,探讨生物等效性试验中生物样品分析的关键问题。
To use bioequivalence study on consistency evaluation is the basis of the generic drug application.Pharmacokinetics is the optimal method used for evaluating bioequivalence. The most important aspect in pharmacokinetic is bioanalysis, which will directly affect the safety and effectiveness of drugs, and is also the key point for the results of bioequivalence study. Previous analytical results suggest that there is great room for improvement in data quality of bioanalysis carried out in our country. Thus, the aim of the study is to discuss the key points of method establishment, validation, testing, and recording in bioanalysis of bioequivalence based on the relevant guidelines and our actual work.
To use bioequivalence study on consistency evaluation is the basis of the generic drug application.Pharmacokinetics is the optimal method used for evaluating bioequivalence. The most important aspect in pharmacokinetic is bioanalysis, which will directly affect the safety and effectiveness of drugs, and is also the key point for the results of bioequivalence study. Previous analytical results suggest that there is great room for improvement in data quality of bioanalysis carried out in our country. Thus, the aim of the study is to discuss the key points of method establishment, validation, testing, and recording in bioanalysis of bioequivalence based on the relevant guidelines and our actual work.
引文
[1]国务院办公厅.国务院办公厅关于开展仿制药质量和疗效一致性评价的意见[EB/OL].北京:国务院办公厅,2016-03-05[2018-5-20].http://www.gov.cn/zhengce/content/2016-03/05/content_5049364.htm.
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[6]朱雪萍.体内药物分析的研究进展[J].中国实用医刊,2011,38(18):114-115.
[7]ROMA?SKI M,G?óWKA F.Clinical bioanalysis of treosulfan and its epoxides:The importance of collected blood processing for valid pharmacokinetic results[J].J Pharm Biomed Anal,2018(153):199-203.
[8]田华.实验室药品标物应用与管理中常见问题分析及建议[J].中国计量,2016(12):46-47.
[9]LI Q,CHEN J Z,GUO R C.Determination of ornidazole in plasma by HPLC and study on its pharmacokinetics and bioequivalence of domestic and imported tablets in 18 healthy volunteers[J].Chin J Mod Appl Pharm(中国现代应用药学),2004,21(2):129-132.
[10]SHAO R,LOU H G,RUAN Z R,et al.Determination of rosuvastatin in human plasma by UPLC-MS/MS and Its application to bioequivalence study[J].Chin J Clin Pharmacol Ther(中国临床药理学与治疗学),2016,21(2):203-209.
[11]FU W,REN X H,CHEN Q,et.al.Pharmacokinetics and bioequivalence of trimebutine maleate sustained-release tablets with multiple dose administration[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(4):462-466.
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[13]WANG Y,ZHOU Y B,TIAN J,et.al.Determination of isosorbide mononitrate in human plasma by gas chromatography with electron capture detector and study on the bioequivalence of Isosorbide Mononitrate tablets[J].JPediatric Pharm(儿科药学杂志),2009,15(4):39-41.
[14]毛姗.GC法测定人血浆中卵磷脂络合碘药物浓度及生物等效性的研究[J].中国实用医药,2015,10(17):140-141.
[15]宋耀虹,冯涛,林其燧.生物素-链霉亲和素免疫学法测定地高辛的研究[J].生物化学与生物物理进展,1997,24(6):565-567.
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[19]INGELSE B,BARROSO B,GRAY N,et al.European Bioanalysis Forum:recommendation on dealing with hemolyzed and hyperlipidemic matrices[J].Bioanalysis,2014,6(23):3113-3120.
[20]WANG H Q,WANG M,LUO Z,et.al.Determination of plasma concentration by UPLC-MS/MS and bioequivalence of two finasteride preparations in human[J].Chin J New Drugs(中国新药杂志).2018,27(4):437-442.
[21]CAI H L,DENG Y,FANG P F,et.al.A sensitive LC-MS/MSmethod for analysis of pericyazine in presence of7-hydroxypericyazine and pericyazine sulphoxide in human plasma and its application to a comparative bioequivalence study in Chinese healthy volunteers[J].J Pharm Biomed Anal.2017(135):67-74.
[22]HU L L,TANG J L,ZHOU S W,et.al.Quantification of roxithromycin in human plasma by UPLC-MS/MS and its application in a pharmacokinetic study[J].China Measurement test(中国测试),2013,39(6):60-63.
[23]HU L L,XU Y,ZHOU J,et.al.Quantification of levetiracetam in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study[J].Chin J Pharm Anal(药物分析杂志),2016,36(4):655-661.
[24]JENJIRATTITHIGARN N,WORACHAT N,HORSUWAN S,et.al.Determination of plasma levetiracetam level by liquid chromatography-tandem mass spectrometry(LC-MS-MS)and its application in pharmacokinetics studies in neonates[J].JChromatogr B Analyt Technol Biomed Life Sci,2018(1085):13-20.
[25]CHEN Z H,FENG S Y,NAN F,et.al.LC-MS/MSDetermination of Tenofovir in Human Plasma and Its Bioequivalence[J].J Sichuan Univ(Med Sci Edi)(四川大学学报:医学版),2018,49(1):107-112.
[26]ZHANG C,WANG L,YANG Y,et.al.Validated LC-MS/MSmethod for the determination of sarpogrelate in human plasma:Application to a pharmacokinetic and bioequivalence study in Chinese volunteers[J].J Pharm Biomed Anal,2010,53(3):546-551.
[27]HUANG M,ZHANG Q Y,ZONG S L,et.al.Rapid determination of losartan in human plasma by LC-MS/MS and study on its bioequivalence[J].Pract Pharm Clin Rem(实用药物与临床),2017,20(4):443-446.
[28]YU L,YANG L,SONG L,et.al.Study on the bioequivalence of Levonorgestrel tablets in healthy volunteers[J].West Chin JPharm Sci(华西药学杂志),2016,31(4):397-400.
[29]BHADORIYA A,DASANDI B,PARMAR D,et.al.Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study[J].JPharm Anal,2018,8(4):271-276.
[30]BHADORIYA A,RATHNAM S,DASANDI B,et.al.Sensitive and rapid determination of amantadine without derivatization in human plasma by LC-MS/MS for a bioequivalence study[J].J Pharm Anal,2018,8(3):202-207.
[31]国家食品药品监管总局.总局关于发布化学药品新注册分类申报资料要求(试行)的通告[EB/OL].北京:国家食品药品监管总局,2016-05-04[2018-05-20].http://www.samr.cfda.gov.cn/WS01/CL0087/151985.html.
[32]MAI L Y,CHEN X,AN J M,et al.Consideration on abbreviate new drug application in U.S.A.and its implication for China[J].Pharm Today(今日药学),2017,27(10):675-682.
[2]国家食品药品监管总局药品审评中心.以药动学参数为终点评价指标的化学药物仿制药人体生物等效性研究技术指导原则[EB/OL].北京:国家食品药品监管总局药品审评中心,2015-11-27[2018-5-20].http://www.cde.org.cn/zdyz.do?method=largePage&id=227.
[3]中国药典.四部[S].2015:363-368.
[4]ZHANG D,LIU M,WANG X L,et.al.Key questions in bioanalysis in bioequivalence study[J].Chin J New Drugs Clin Rem(中国新药与临床杂志),2014,33(3):157-163.
[5]WEI M J,LI K X.Bioanalysis performed according to regulations and guidelines[J].Chin J Anal Pharm(药物分析杂志),2014,34(1):12-16.
[6]朱雪萍.体内药物分析的研究进展[J].中国实用医刊,2011,38(18):114-115.
[7]ROMA?SKI M,G?óWKA F.Clinical bioanalysis of treosulfan and its epoxides:The importance of collected blood processing for valid pharmacokinetic results[J].J Pharm Biomed Anal,2018(153):199-203.
[8]田华.实验室药品标物应用与管理中常见问题分析及建议[J].中国计量,2016(12):46-47.
[9]LI Q,CHEN J Z,GUO R C.Determination of ornidazole in plasma by HPLC and study on its pharmacokinetics and bioequivalence of domestic and imported tablets in 18 healthy volunteers[J].Chin J Mod Appl Pharm(中国现代应用药学),2004,21(2):129-132.
[10]SHAO R,LOU H G,RUAN Z R,et al.Determination of rosuvastatin in human plasma by UPLC-MS/MS and Its application to bioequivalence study[J].Chin J Clin Pharmacol Ther(中国临床药理学与治疗学),2016,21(2):203-209.
[11]FU W,REN X H,CHEN Q,et.al.Pharmacokinetics and bioequivalence of trimebutine maleate sustained-release tablets with multiple dose administration[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(4):462-466.
[12]BHADORIYA A,DASANDI B,PARMAR D,et al.Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study[J].JPharm Anal,2018,8(4):271-276.
[13]WANG Y,ZHOU Y B,TIAN J,et.al.Determination of isosorbide mononitrate in human plasma by gas chromatography with electron capture detector and study on the bioequivalence of Isosorbide Mononitrate tablets[J].JPediatric Pharm(儿科药学杂志),2009,15(4):39-41.
[14]毛姗.GC法测定人血浆中卵磷脂络合碘药物浓度及生物等效性的研究[J].中国实用医药,2015,10(17):140-141.
[15]宋耀虹,冯涛,林其燧.生物素-链霉亲和素免疫学法测定地高辛的研究[J].生物化学与生物物理进展,1997,24(6):565-567.
[16]毛耀南,钱南萍.微生物法测定硫酸阿米卡星血药浓度[J].现代医药卫生,2007,23(7):1051-1052.
[17]US Food and Drug Administration,Center for Drug Evaluation and Research.Center for Veterinary Medicine.Guidance for industry:bioanalytical method validation[EB/OL].New Hampshire,US Food and Drug Administration,2001-05[2018-5-20].http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf.
[18]European Medicines Agency.Guideline on validation of bioanalytical methods[EB/OL].London,European Medicines Agency,2011-07-21[2018-5-20].http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/08/WC500109686.pdf.
[19]INGELSE B,BARROSO B,GRAY N,et al.European Bioanalysis Forum:recommendation on dealing with hemolyzed and hyperlipidemic matrices[J].Bioanalysis,2014,6(23):3113-3120.
[20]WANG H Q,WANG M,LUO Z,et.al.Determination of plasma concentration by UPLC-MS/MS and bioequivalence of two finasteride preparations in human[J].Chin J New Drugs(中国新药杂志).2018,27(4):437-442.
[21]CAI H L,DENG Y,FANG P F,et.al.A sensitive LC-MS/MSmethod for analysis of pericyazine in presence of7-hydroxypericyazine and pericyazine sulphoxide in human plasma and its application to a comparative bioequivalence study in Chinese healthy volunteers[J].J Pharm Biomed Anal.2017(135):67-74.
[22]HU L L,TANG J L,ZHOU S W,et.al.Quantification of roxithromycin in human plasma by UPLC-MS/MS and its application in a pharmacokinetic study[J].China Measurement test(中国测试),2013,39(6):60-63.
[23]HU L L,XU Y,ZHOU J,et.al.Quantification of levetiracetam in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study[J].Chin J Pharm Anal(药物分析杂志),2016,36(4):655-661.
[24]JENJIRATTITHIGARN N,WORACHAT N,HORSUWAN S,et.al.Determination of plasma levetiracetam level by liquid chromatography-tandem mass spectrometry(LC-MS-MS)and its application in pharmacokinetics studies in neonates[J].JChromatogr B Analyt Technol Biomed Life Sci,2018(1085):13-20.
[25]CHEN Z H,FENG S Y,NAN F,et.al.LC-MS/MSDetermination of Tenofovir in Human Plasma and Its Bioequivalence[J].J Sichuan Univ(Med Sci Edi)(四川大学学报:医学版),2018,49(1):107-112.
[26]ZHANG C,WANG L,YANG Y,et.al.Validated LC-MS/MSmethod for the determination of sarpogrelate in human plasma:Application to a pharmacokinetic and bioequivalence study in Chinese volunteers[J].J Pharm Biomed Anal,2010,53(3):546-551.
[27]HUANG M,ZHANG Q Y,ZONG S L,et.al.Rapid determination of losartan in human plasma by LC-MS/MS and study on its bioequivalence[J].Pract Pharm Clin Rem(实用药物与临床),2017,20(4):443-446.
[28]YU L,YANG L,SONG L,et.al.Study on the bioequivalence of Levonorgestrel tablets in healthy volunteers[J].West Chin JPharm Sci(华西药学杂志),2016,31(4):397-400.
[29]BHADORIYA A,DASANDI B,PARMAR D,et.al.Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study[J].JPharm Anal,2018,8(4):271-276.
[30]BHADORIYA A,RATHNAM S,DASANDI B,et.al.Sensitive and rapid determination of amantadine without derivatization in human plasma by LC-MS/MS for a bioequivalence study[J].J Pharm Anal,2018,8(3):202-207.
[31]国家食品药品监管总局.总局关于发布化学药品新注册分类申报资料要求(试行)的通告[EB/OL].北京:国家食品药品监管总局,2016-05-04[2018-05-20].http://www.samr.cfda.gov.cn/WS01/CL0087/151985.html.
[32]MAI L Y,CHEN X,AN J M,et al.Consideration on abbreviate new drug application in U.S.A.and its implication for China[J].Pharm Today(今日药学),2017,27(10):675-682.
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