QUANTITATIVE-DETERMINATION OF PERPHENAZINE AND ITS METABOLITES IN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND COULOMETRIC DETECTION

An accurate, reliable method has been developed for the therapeutic mo nitoring of perphenazine (PPZ) and its major metabolites in human plas ma samples. Steady-state plasma levels of PPZ and, its metabolites wer e quantitated for 30 elderly patients (mean age: 75) undergoing concur rent treatment with nortriptyline (NT) and, PPZ, doses ranging from 4 to 32 mg/day for PPZ. The assay was suitable with patients on concurre nt medications, and smaller patient plasma volumes (1 ml) were used in dicating sufficient sensitivity and specificity. After plasma extracti on and separation on a Nucleosil 5-mu m C-18 column, the recoveries (m ean +/-S.D.) of PPZ and its metabolites were determined; perphenazine 92 +/- 7.5%, deshydroxyethylperphenazine 81 +/- 7.2%, perphenazine sul foxide 68 +/- 6.4%, and 7-hydroxyperphenazine 45 +/- 5.5%. The assay a lso had limits of quantitative detectability for PPZ and its metabolit es 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 reprodu cibility of this method should improve PPZ therapeutic drug monitoring and research on interactions in depressed geriatric patients.