Development of a sensitive and fast UHPLC-MS/MS method for determination of clopidogrel, clopidogrel acid and clopidogrel active metabolite H4 in human plasma

被引：9

作者：

Hua, Wenyi ^{[1
]}

Lesslie, Michael ^{[1
]}

Hoffman, Brian T. ^{[1
]}

Binns, Christopher ^{[1
]}

Mulvana, Daniel ^{[1
]}

机构：

[1] Quintiles, Bioanalyt & ADME Labs, Ithaca, NY 14850 USA

来源：

BIOANALYSIS | 2015年 / 7卷 / 12期

关键词：

THIOL METABOLITE; QUANTITATIVE-DETERMINATION; SAMPLES;

D O I：

10.4155/bio.15.82

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Quantitation of CAM H4 in biological matrix has been a challenge due to low concentrations, instability and the existence of four CAM diastereomers. Historically, either inactive clopidogrel acid or CAM diastereomers without separation were measured for exposure and PK parameters. Results: This study presents a sensitive and fast UHPLC-MS/MS method for simultaneous quantitation of clopidogrel, clopidogrel acid and active metabolite H4 in human plasma. The method demonstrated the separation of H4 from other isomers and yet retained clopidogrel acid. Matrix stabilities, accuracy and precision, recovery and matrix effect were evaluated during development. Conclusion: With LLOQ of 0.05 ng/ml for clopidogrel and H4, and 5.5 min LC gradient, it is the most sensitive and fastest method to our knowledge.

引用

页码：1471 / 1482

页数：12

共 17 条

[11] Development and validation of an HPLC-MS/MS method to quantify clopidogrel acyl glucuronide, clopidogrel acid metabolite, and clopidogrel in plasma samples avoiding analyte back-conversion [J].

Silvestro, Luigi ;

Gheorghe, Mihaela ;

Iordachescu, Adriana ;

Ciuca, Valentin ;

Tudoroniu, Ariana ;

Savu, Simona Rizea ;

Tarcomnicu, Isabela .

ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2011, 401 (03) :1023-1034

[12] Development and validation of an HPLC-MS/MS method to determine clopidogrel in human plasma. Use of incurred samples to test back-conversion [J].

Silvestro, Luigi ;

Gheorghe, Mihaela Cristina ;

Tarcomnicu, Isabela ;

Savu, Silviu ;

Savu, Simona Rizea ;

Iordachescu, Adriana ;

Dulea, Constanta .

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2010, 878 (30) :3134-3142

[13] Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS [J].

Takahashi, Makoto ;

Pang, Henrianna ;

Kawabata, Kiyoshi ;

Farid, Nagy A. ;

Kurihara, Atsushi .

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2008, 48 (04) :1219-1224

[14] An improved method for specific and quantitative determination of the clopidogrel active metabolite isomers in human plasma [J].

Tuffal, Gilles ;

Roy, Sebastien ;

Lavisse, Melanie ;

Brasseur, Denis ;

Schofield, Joe ;

Touchard, Nathalie Delesque ;

Savi, Pierre ;

Bremond, Nicolas ;

Rouchon, Marie-Claude ;

Hurbin, Fabrice ;

Sultan, Eric .

THROMBOSIS AND HAEMOSTASIS, 2011, 105 (04) :696-705

[15]

US Department of Health and Human Services, GUID IND BIOAN METH

[16] Prasugrel achieves greater and faster P2Y12 receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease [J].

Wallentin, Lars ;

Varenhorst, Christoph ;

James, Stefan ;

Erlinge, David ;

Braun, Oscar Oe ;

Jakubowski, Joseph A. ;

Sugidachi, Atsuhiro ;

Winters, Kenneth J. ;

Siegbahn, Agneta .

EUROPEAN HEART JOURNAL, 2008, 29 (01) :21-30

[17] Formation of the Thiol Conjugates and Active Metabolite of Clopidogrel by Human Liver Microsomes [J].

Zhang, Haoming ;

Lau, Wei C. ;

Hollenberg, Paul F. .

MOLECULAR PHARMACOLOGY, 2012, 82 (02) :302-309

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