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Arzneimittelforschung 2011; 61(6): 353-357
DOI: 10.1055/s-0031-1296210
Anticoagulants · Antithrombotics · Anti-varicosis Drugs · Blood Flow Stimulants
Editio Cantor Verlag Aulendorf (Germany)

Study on bioavailability difference between clopidogrel bisulfate form I and form II using liquid chromatography/tandem mass spectrometry

Qiao-Gen Zou
1   Biology and Pharmacy Engineer Department, Nanjing University of Technology, Nanjing, (P. R. China)
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, (P. R. China)
,
Xiao-Heng Tan
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, (P. R. China)
,
Wen-Jun Che
3   Administration for Products Quality Supervision and Inspection of Jiangsu Province, Nanjing, (P. R. China)
,
Zun-Jian Zhang
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, (P. R. China)
,
Ping Wei
1   Biology and Pharmacy Engineer Department, Nanjing University of Technology, Nanjing, (P. R. China)
,
Ping-Kai Ou-Yang
1   Biology and Pharmacy Engineer Department, Nanjing University of Technology, Nanjing, (P. R. China)
› Author Affiliations
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Publication History

Publication Date:
27 November 2011 (online)

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Abstract

The bioavailability of clopidogrel bisulfate (CAS 135046-48-9) form I was compared with that of Clopidogrel bisulfate form II in 12 male Sprague-Dawley rats. The rats, randomly divided into two groups, received a single oral dose of 8 mg/kg Clopidogrel (CP) bisulfate form I and form II, respectively, under fasting condition. The plasma concentrations of CP and its inactive carboxylic acid metabolite (CAS 144457-28-3, IM) were simultaneously determined by a sensitive, specific LC-MS/MS method. The pharmacokinetic parameters included Cmax, Tmax, t1/2, AUC0–t AUC0–∞. The AUC0–∞ of CP was 13.78 ± 0.67 and 11.46 ± 1.98 ng/mL · h for CP form I and form II, respectively. The AUC0–∞ of IM was 33.08 ± 5.76 and 21.67 ± 8.95 μg/mL · h for CP form I and form II, respectively. The maximum plasma concentration (Cmax) of CP was 3.81 ± 0.54 ng/mL for CP form I and 3.18 ± 0.31 ng/mL for CP form II, the Cmax of IM was 3.42 ± 0.41 and 2.08 ± 0.68 μg/mL for the CP form I and form II, respectively. There was an obvious difference between form I and form II for Cmax and the area under the plasma concentration time curve for both CP and IM after a t-test. This study shows that CP form I has better bioavailability in rats than CP form II.

Key words

Antiplatelet drug - Bioavailability - Clopidogrel bisulfate - Clopidogrel carboxylic acid metabolite - LC-MS/MS - Solid form
 

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