DETERMINATION OF THE CALCIUM-ANTAGONIST SIM6080 AND ITS N-DEMETHYLATED AND O-DEMETHYLATED METABOLITES IN PLASMA, URINE AND TISSUES BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

A sensitive and versatile high-performance liquid chromatographic assa y for the determination of the calcium antagonist SIM6080 and its four N- and O-demethylated metabolites in plasma, urine and tissues has be en developed and validated. A two-step extraction procedure is employe d followed by reversed-phase liquid chromatographic analysis using ult raviolet detection. An isomer of SIM6080 was used as the internal stan dard. The analysis of spiked plasma, urine and tissues demonstrated th e accuracy and precision of the assay with quantitation limits of 5 ng /ml (plasma and urine) or 100 ng/g (tissues). This assay has been used for urinary recovery and tissue distribution studies, as well as for toxicokinetic protocols.