A rapid gas chromatographic method quantitating clozapine in human plasma or serum for the purpose of therapeutic monitoring.
A gas chromatographic method using nitrogen-phosphorus detection was developed to quantitate clozapine in plasma or serum. Methyl clonazepam was used as an internal standard. Sample preparation included a single-step extraction with ethyl acetate, which was injected directly onto a wide-bore capillary column. Within-run and total precision, measured as percent coefficient of variation, were determined at low, therapeutic, and high clozapine plasma concentrations. The within-run precision for the low, therapeutic, and high clozapine plasma samples was 5.2, 2.7, and 2.4%, respectively. The total precision for the low, therapeutic, and high clozapine plasma samples was 10.0, 2.6, and 2.0%, respectively. Analytical accuracy was evaluated by comparing quantitative results with those obtained from a reference laboratory. Those samples containing therapeutic or high concentrations agreed within 3%; the sample containing a subtherapeutic concentration differed by 11.9%. The limit of quantitation was determined to be 35 ng/mL, and the upper limit of linearity was 3000 ng/mL. No significant interferences were detected after testing more than two dozen drugs and metabolites.
Jennison
T A
TA
Associated Regional and University Pathologists, Inc., Salt Lake City, UT 84108, USA.
Brown
P
P
Crossett
J
J
Kushnir
M
M
Urry
F M
FM
D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D002849:Chromatography, Gas / Q000379:methods*; D002998:Clonazepam / Q000097:blood; D003024:Clozapine / Q000097:blood* / Q000627:therapeutic use; D004347:Drug Interactions; D016903:Drug Monitoring; D006801:Humans; D008745:Methylation; D012015:Reference Standards; D015203:Reproducibility of Results
D014150:Antipsychotic Agents; D002998:Clonazepam; D003024:Clozapine