Gas-ChromatographicAnalysisfor Chiorpromazineand Some of Its Metabolitesin HumanSerum, with Use of a NitrogenDetector

We describe a gas-chromatographic method for measuring chiorpromazine and its metabolites chiorpromazine sulfoxide, mono-N-desmethylchlorpromazine, and di-Ndesmethylchlorpromazine at therapeutic concentrations in human serum, with use of a nitrogen detector. The compounds are extracted from serum at pH 10.5 into hexane/isoamyl alcohol, re-extracted into dilute HCI, and then extracted into hexane after alkalinization of the HCI. The N-desmethylated metabolites are measured as their respective N-trifluoroacetyl derivatives; the parent drug and its sulfoxide are measured as the unchanged bases. Promazine is the internal standard. As little as 5 tg of chlorpromazine, 20 ig of chiorpromazine sulfoxide, 20 g of mono-N-desmethylchlorpromazine, and 10 g of di-N-desmethylchlorpromazine per liter can be measured in 2-mL samples of serum. The within-run coefficients of variation for assays of these drugs at 100 g/L are 2.7%, 5.6%, 5.1%, and5.3%, respectively. The procedure was applied to patients receiving therapeutic doses of chlorpromazine and to patients who had ingested an overdose of chlorpromazine.