title: Study on bioavailability difference between clopidogrel bisulfate form I and form II using liquid chromatography/tandem mass spectrometry.
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 C(max), T(max), t1/2, AUC(0-t), AUC(0-infinity). The AUC(0-infinity) of CP was 13.78 +/- 0.67 and 11.46 +/- 1.98 ng/ mL x h for CP form I and form II, respectively. The AUC(0-infinity) of IM was 33.08 +/- 5.76 and 21.67 +/- 8.95 microg/mL x 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 microg/ 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.
authors.affiliation: Biology and Pharmacy Engineer Department, Nanjing University of Technology, Nanjing, PR China
authors.forename: Qiao-Gen
authors.initials: QG
authors.lastname: Zou
authors.forename: Xiao-Heng
authors.initials: XH
authors.lastname: Tan
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Che
authors.forename: Zun-Jian
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Ping-Kai
authors.initials: PK
authors.lastname: Ou-Yang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D000069059:Atorvastatin; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D000077144:Clopidogrel; D006207:Half-Life; D006538:Heptanoic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000077144:Clopidogrel; D013988:Ticlopidine