Determination of SR26334 in rats plasma by LC-MS/MS and study of its pharmacokinetics

OBJECTIVE To develop a LC-MS /MS method for the determination of Clopidogrel carboxylic acid metabolites SR26334 in rat plasma and study of its pharmacokinetidcs.METHODS The plasma was extracted by ethyl acetate and n-hexane.The analytical column was packed with ZORBAX SB-C18.The mobile phase were acetoni-trile-0.1% formic acid solution and the flow rate was 0.3mL.min-1,with electrospray positive ionization(ESI +) and multiple reaction monitoring(m / z 308.1 →m/z 198.1(SR26334) and m/z 383.2→337.0(Loratadine)).Six Wistar male rats were given a single 7.5mg.kg-1 oral dose of Clopidogrel.Blood samples were collected from the tail vein at different time points after oral administration.The concentration of SR26334 in plasma were detected by this LC-MS / MS methods.The pharmacokinetics parameters were analyzed by DAS program.RESULTS Excellent liner relationship was obtained from the range of 1ng.mL-1 to 5000ng.mL-1(r =0.9991),the limit determination of SR26334 was 1ng.mL-1.The average recovery was more than 97% and the average extraction recovery was above 85%.The inter-and intra-day RSD were less than 8%.CONCLUSION The method is accurate,simple,rapid and could be used to determine the SR26334 concentration in rat plasma and for study of its pharmacokinetics.