A rapid gas chromatographic method quantitating clozapine in human plasma or serum for the purpose of therapeutic monitoring

J Anal Toxicol. 1995 Nov-Dec;19(7):537-41. doi: 10.1093/jat/19.7.537.

Abstract

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.

MeSH terms

  • Antipsychotic Agents / blood*
  • Antipsychotic Agents / therapeutic use
  • Chromatography, Gas / methods*
  • Clonazepam / blood
  • Clozapine / blood*
  • Clozapine / therapeutic use
  • Drug Interactions
  • Drug Monitoring*
  • Humans
  • Methylation
  • Reference Standards
  • Reproducibility of Results

Substances

  • Antipsychotic Agents
  • Clonazepam
  • Clozapine