DETERMINATION OF PIRENZEPINE IN HUMAN PLASMA USING LIQUID-CHROMATOGRAPHY WITH TANDEM MASS-SPECTROMETRIC DETECTION

A sensitive (LOQ = 1 ng ml(-1)) and specific method based on liquid ch romatography with tandem mass spectrometric (MS/MS) detection has been developed and validated for the analysis of pirenzepine (I) in plasma . Sample preparation involved liquid-liquid extraction of drug and int ernal standard (IS) from basified plasma. The organic extract was evap orated to dryness, and the residue was reconstituted in the mobile pha se and then injected into the liquid chromatography/MS/MS system. Drug , IS, and endogenous impurities were separated using reverse-phase chr omatography. A Sciex API III tandem mass spectrometer equipped with a heated nebulizer was operated in the positive ion mode. Multiple react ion monitoring using the parent-->daughter ion combinations of mit 352 -->113 and 629-->422 was used to quantify I and IS, respectively. The method was validated in the concentration range of 1-100 ng ml(-1) pla sma with adequate assay precision and accuracy, and was utilized to su pport human safety and tolerability study with I.