Quantitative determination of perphenazine and its metabolites in plasma by high-performance liquid chromatography and coulometric detection

Abstract

An accurate, reliable method has been developed for the therapeutic monitoring of perphenazine (PPZ) and its major metabolites in human plasma samples. Steady-state plasma levels of PPZ and its metabolites were quantitated for 30 elderly patients (mean age: 75) undergoing concurrent treatment with nortriptyline (NT) and PPZ, doses ranging from 4 to 32 mg/day for PPZ. The assay was suitable with patients on concurrent medications, and smaller patient plasma volumes (1 ml) were used indicating sufficient sensitivity and specificity. After plasma extraction and separation on a Nucleosil 5-microns C18 column, the recoveries (mean +/- S.D.) of PPZ and its metabolites were determined; perphenazine 92 +/- 7.5%, deshydroxyethylperphenazine 81 +/- 7.2%, perphenazine sulfoxide 68 +/- 6.4%, and 7-hydroxyperphenazine 45 +/- 5.5%. The assay also had limits of quantitative detectability for PPZ and its metabolites as follows: perphenazine 0.5 ng/ml, deshydroxyethylperphenazine 1.0 ng/ml, perphenazine sulfoxide 0.5 ng/ml, and 7-hydroxyperphenazine 5 ng/ml. Inter-assay reproducibility (C.V.) for the quality controls and patient samples ranged from 18.8 to 2.4%. The sensitivity and reproducibility of this method should improve PPZ therapeutic drug monitoring and research on interactions in depressed geriatric patients.