Clozapine dose-concentration relationships in plasma, hair and sweat specimens of schizophrenic patients

The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily dose of clozapine deli vered to patients. Twenty-six subjects treated with clozapine at 200-700 mg /day for refractory psychosis were included in the study. Clozapine was det ermined in plasma by liquid chromatography coupled to a diode array detecti on system, after extraction with an organic solvent at pH 9.5. Clozapine wa s extracted from hair and sweat patches specimens by incubation in methanol overnight at 40 degrees C. The residues were analyzed by gas chromatograph y coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in concentrations ranging from 30 to 1016 ng/ml in plasma (n=22), from 0.17 to 34.24 ng/mg in hair (n=23) and f rom 49 to 5609 ng/ patch in sweat (n=20). Preliminary results suggest a lac k of correlation between daily regimen of clozapine and plasma levels of th e drug. Therefore, a better dose-concentration relationship was observed in our study between daily dose and hair concentration (r=0.542, P<7%) or bet ween daily dose and sweat concentration (r=0.589, P<6%), but with wide vari ations for patients at the same posology. However, the idea of using quanti tative drug measurements in hair or sweat to ascertain whether a patient ha s taken his treatment exactly as prescribed will remain inapplicable. (C) 2 000 Elsevier Science Ireland Ltd. All rights reserved.