Simultaneous determination of four antipsychotic drugs in plasma by high-performance liquid chromatography: Application to management of acute intoxications

A specific reversed phase-high pressure liquid chromatography (RP-HPLC) method has been developed for the simultaneous determination of clozapine (CZP), loxapine (LXP), zuclopenthixol (ZPT) and flupenthixol (FPT) in plasma. These four antipsychotic drugs are frequently used for the treatment of schizophrenia and other neuropsychiatric diseases. Carpipramine, a dihydrodibenzazepine, was used as an internal standard (I.S.). A liquid–liquid procedure was used to extract the drugs from human plasma. The analysis was performed on a XTerra™ MS C18 column with UV detection. Calibration curves were linear in the range 50–1000 μg/l. The limit of quantification (LOQ) was 15 μg/l for clozapine and loxapine and 20 μg/l for zuclopenthixol and flupenthixol. The coefficient of variation (CV) for intra- and inter-day precision was 7.2% or less with accuracies within 10% for the three concentrations. socratic and rapid method (run time<10 min) is useful for the management of acute intoxication.