Determination of clozapine and its major metabolites in serum samples of adolescent schizophrenic patients by high-performance liquid chromatography. Data from a prospective clinical trial.
This report describes a method for determination of clozapine and its major metabolites N-desmethylclozapine and clozapine N-oxide in serum samples of adolescent schizophrenic patients during maintenance therapy. The method includes deproteinization and subsequent high-performance liquid chromatography with electrochemical detection. The method shows sufficient sensitivity to quantitate clozapine, clozapine N-oxide and N-desmethylclozapine accurately at 0.5, 5, and 0.5 ng/ml, respectively. We were able to demonstrate for 16 patients receiving fixed doses of clozapine that the individual mean values calculated from six consecutive measurements revealed a strong linear dosage and serum level relationship (Pearson's coefficient of correlation): clozapine (r = 0.82, p = 0.0001); N-desmethylclozapine (r = 0.81, p = 0.0001); clozapine N-oxide (r = 0.91; p = 0.0001). Preliminary pharmacokinetic data are presented and dose-response relationship are discussed.
Schulz
E
E
Department of Child and Adolescent Psychiatry, Philipps University, Marburg, Germany.
Fleischhaker
C
C
Remschmidt
H
H
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003024:Clozapine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy*
D003024:Clozapine