High-performance liquid chromatographic analysis of the D4 receptor antagonist SCH 66712 in rat plasma

SCH 66712 is a potent and selective dopamine D4 receptor antagonist. An HPLC 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 involved solid-phase extraction on an ethyl cartridge and HPLC separation on a reversed-phase C8 column with quantitation using a fluorescence detector. The calibration curve was linear over a concentration range of 5-100 ng/ml. The 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 satisfactory as indicated by an intra-day C.V. of < or = 4% and an inter-day C.V. of < or = 6%. The accuracy was also satisfactory as shown by an intra-day bias of < or = 8% and an inter-day bias of < or = 9%. The assay was shown to be sensitive, specific, accurate, precise, and reliable for use in pharmacokinetic or toxicokinetic studies.