Abstract:A spectrophotometric method for the quantitative determination of chlorprothixene (CPT) and its metabolites in autopsy material has been developed. The method involves repeated extractions with non‐polar solvents at pH 11–12 and thin‐layer chromatographic separation, followed by u.v. spectrophotometry of hydrochloric acid‐methanol extracts of the chromatographic fractions. The method which has a lower detection limit of 0.1 μ/g material, was used for blood, urine and liver from 12 cases, in which CPT was considered as the only or contributory cause of death. In the cases in which death occurred due to CPT only (2.5–4 g of CPT orally), the total concentration of thioxanthenes (i.e. CPT and its metabolites) were 0–1 μg/mg in the blood, 0.1–15 μg/ml in the urine and 22–86 μg/g in the liver. This indicates an extremely uneven distribution of thioxanthenes in the body. In addition to unchanged CPT, 5 thioxanthene metabolites were detected in the material. Three metabolites were identified as chlorprothixen‐sulphoxide, N‐monodemethylchlorprothixene and N‐monodemethylchlorprothix‐cnsulphoxide, respectively. The two unidentified thioxanthenes on the basis of their u. v. absorption spectra were assumed to be a sulphoxide and a non‐sulphoxide metabolite of CPT. It is concluded that CPT is a more toxic drug than previously believed, and that the total concentration of thioxanthenes in the liver is the most suitable parameter for the toxicological evalu