Liquid chromatography tandem mass spectrometry method for the quantification of Sarpogrelate, a selective 5-HT2A receptor antagonist, in plasma: application to a pre-clinical pharmacokinetic study

A simple LC-MS/MS method was developed and validated for the estimation of sarpogrelate in 50 mu L of rat plasma The analyte and internal standard (IS) were extracted from rat plasma by acetonitrile precipitation and they were separated on a reversed-phase C-8 column with gradient program The MS acquisition was performed with multiple reaction monitoring mode using m/z 430 2 to m/z 135 0 for analyte and m/z 448 2 to m/z 285 3 for IS The calibration curves were linear over the range of 1-1000 ng/mL with the correlation coefficient greater than 0 999 With dilution integrity up to 20-fold, the upper limit of quantification was extendable up to 15,000 ng/mL The method was successfully applied to the analysis of rat plasma samples after single dose oral administration of sarpogrelate at 5 mg/kg to rats for the determination of its pharmacokinetics Following oral administration the maximum mean concentration in plasma (C-max, 11514 ng/mL) was achieved at 025 h (T-max) and the area under curve (AUC(0-24)) was 11051 +/- 3315 ng h/mL The half-life (t(1/2)) and clearance (Cl) were 2 9 +/- 11 h and 490 +/- 171 mL/h/kg, respectively We believe that development of a method in rodent plasma would facilitate the ease of adaptability of sarpogrelate in human plasma Copyright (C) 2010 John Wiley & Sons, Ltd