Determination of an antipsychotic agent (ICI 204,636) and its 7-hydroxy metabolite in human plasma by high-performance liquid chromatography and gas chromatography-mass spectrometry.

R H Pullen, K M Palermo, M A Curtis

文献索引：J. Chromatogr. A. 573(1) , 49-57, (1992)

全文：HTML全文

摘要

ICI 204,636 (I) is an orally active antipsychotic agent under development for the treatment of schizophrenia in humans. It is partially converted in animals to an active 7-hydroxy metabolite (II). Methods were developed for the simultaneous determination of both analytes in human plasma using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The analytes were extracted from plasma using phenyl solid-phase extraction columns. Quantification by isocratic HPLC was performed in the reversed-phase mode with detection at 250 nm. Extracts were derivatized to trimethylsilyl ethers for quantification by GC-MS using selected-ion monitoring. Both assays were evaluated for consistency of response, precision, accuracy and specificity. Limits of quantification for I and II by HPLC were 15 and 20 ng/ml, respectively; limits of quantification for I and II by GC-MS were 2 and 5 ng/ml, respectively. Both methods were applied to the analysis of clinical samples from oral dosing studies with I.