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

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 8mg/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 C_max, T_max, t_1/2, AUC_0-t, AUC _0-∞. The AUC_0-∞ of CP was 13.78 ± 0.67 and 11.46 ± 1.98 ng/mL·h for CP form I and form II, respectively. The AUC_0-∞ 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 (C_max) 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 C_max 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 C_max 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.