Liquid chromatographic analysis of the cis( Z)- and trans( E)-isomers of clopenthixol in human plasma using a novel solid phase extraction procedure

Abstract

A simple and highly sensitive high-performance liquid chromatographic (HPLC) method for the simultaneous determination of cis( Z)-clopenthixol and trans( E)-clopenthixol in human plasma has been developed. The chromatographic analysis was carried out isocratically on a reversed-phase column (C 8 150×4.6 mm I.D., 5 μm) using a mixture of 25 m M phosphate buffer and acetonitrile (65:35 v/v, pH* 3.0) as the mobile phase, and ultraviolet detection at 230 nm. Plasma sample pretreatment was accomplished by means of an original solid-phase extraction (SPE) procedure carried out on cyanopropyl cartridges, with a high extraction yield and good selectivity. Under the optimum conditions, calibration graphs of spiked human plasma samples were obtained over the concentration ranges 1–300 ng ml −1 for cis( Z)-clopenthixol and 1–200 ng ml −1 for trans( E)-clopenthixol. The limit of detection (LOD) was 0.3 ng ml −1 for both cis( Z)- and trans( E)-isomers of clopenthixol. The method was successfully applied to the determination of cis( Z)-clopenthixol and trans( E)-clopenthixol in plasma samples of schizophrenic patients undergoing therapy with zuclopenthixol.