High-performance liquid chromatographic analysis of the D-4 receptor antagonist SCH 66712 in rat plasma

SCH 66712 is a potent and selective dopamine D-4 receptor antagonist. An HP LC method was developed for the analysis of SCH 66712 in the plasma of rats , a species used for safety evaluation of this compound. The method involve d solid-phase extraction on an ethyl cartridge and HPLC separation on a rev ersed-phase C-8 column with quantitation using a fluorescence detector. The calibration curve was linear over a concentration range of 5-100 ng/ml, Th e limit of quantitation was 5 ng/ml, where the coefficient of variation (C. V.) was 2.9% and the bias was 6%. The precision of the method was satisfact ory as indicated by an intra-day C.V. of less than or equal to 4% and an in ter-day C.V. of less than or equal to 6%. The accuracy was also satisfactor y as shown by an intra-day bias of less than or equal to 8% and an inter-da y bias of less than or equal to 9%. The assay was shown-to be sensitive, sp ecific, accurate, precise, and reliable for use in pharmacokinetic or toxic okinetic studies. (C) 1999 Elsevier Science B.V. All rights reserved.