A rapid and sensitive liquid chromatography tandem mass spectrometry method has been developed and validated for the determination of the active metabolite (R-138727) of prasugrel in human plasma. Because R-138727 contains a thiol group, it requires stabilization by derivatizing with N-ethyl maleimide. Commercially available trandolapril was used as the internal standard (IS). The derivatives of R-138727 and IS were extracted from human plasma using a liquid-liquid extraction technique. Chromatography was performed on a Hypurity C18, 5 µ (50 mm × 4.6 mm, i.d.) column, with the mobile phase consisting of acetonitrile and 10 mM ammonium formate (pH 3.0, 50:50 V/V), followed by detection using mass spectrometry. No significant endogenous peaks corresponding to R-138727 or IS were detected in the blank human plasma samples and no significant matrix effect was observed for R-138727 and IS in the human plasma samples. The mean recovery for R-138727 ranged from 90.1 to 104.1%, with the lower limit of quantification set at 1 ng/ml. Linearity was established for concentrations in the range of 1.0-500.12 ng/ml, with a coefficient of determination (r(2) ) of 0.9958. The derivatized R-138727 was stable in human plasma for 3 months at -20 °C. This method increased the sensitivity and selectivity, resulting in high-throughput analysis of R-138727 using trandolapril as the IS in pharmacokinetic and bioequivalence studies, with a chromatographic run time of 3.7 min.
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