Gas-chromatographic analysis for chlorpromazine and some of its metabolites in human serum, with use of a nitrogen detector.

Abstract

Abstract We describe a gas-chromatographic method for measuring chlorpromazine and its metabolites chlorpromazine sulfoxide, mono-N-desmethylchlorpromazine, and di-N-desmethylchlorpromazine 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 HCl, and then extracted into hexane after alkalinization of the HCl. The N-desmethylated metabolites are measured as their respective N-trifuloracetyl derivatives; the parent drug and its sulfoxide are measured as the unchanged bases. Promazine is the internal standard. As little as 5 micrograms of chlorpromazine, 20 micrograms of chlorpromazine sulfoxide, 20 micrograms of mono-N-desmethylchlorpromazine, and 10 micrograms 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 micrograms/L are 2.7%, 5.6%, 5.1%, and 5.3%, respectively. The procedure was applied to patients receiving therapeutic doses of chlorpromazine and to patients who had ingested an overdose of chlorpromazine.