Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma.
A high-performance liquid chromatographic method has been developed for the simultaneous determination of classical neuroleptics (chlorpromazine, haloperidol, loxapine and clotiapine), atypical antipsychotics (clozapine, quetiapine and risperidone) and their active metabolites (N-desmethylclozapine, clozapine N-oxide and 9-hydroxyrisperidone) in human plasma. Separation was obtained by using a C8 reversed-phase column and a mobile phase composed of 70% aqueous phosphate buffer containing triethylamine at pH 3.0 and 30% acetonitrile. The UV detector was set at 238 nm and amitriptyline was used as the internal standard. A careful pre-treatment procedure of plasma samples was developed, using solid-phase extraction with cyanopropyl cartridges, which gives high extraction yields (>or=93%). The limits of quantitation (LOQ) were always lower than 2.6 ng mL-1 and the limits of detection (LOD) were always lower than 0.9 ng mL-1 for all analytes. The method was applied with success to plasma samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotics. Precision data and accuracy results were satisfactory and no interference from other central nervous system (CNS) drugs was found. Hence the method is suitable for the therapeutic drug monitoring (TDM) of the analytes in psychotic patients' plasma.
Mercolini
Laura
L
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126, and Mental Health Department, M. Malpighi Hospital, Bologna, Italy.
Grillo
Maria
M
Bartoletti
Claudio
C
Boncompagni
Giancarlo
G
Raggi
Maria Augusta
MA
D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D006801:Humans; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
D014150:Antipsychotic Agents