Solid-phase extraction and high-performance liquid chromatographic analysis of clozapine and norclozapine in human plasma.
A rapid high-performance liquid chromatographic method for the simultaneous quantitation of plasma clozapine and its principal metabolite, norclozapine, was developed using a Spherisorb C8 5-micron reverse-phase column and an acetonitrile/potassium phosphate buffer/triethylamine mobile phase. Clozapine and norclozapine were extracted from plasma on solid-phase reusable microcolumns. Absolute recovery of clozapine, norclozapine, and the internal standard, flurazepam, was quantitative. The mean intraassay coefficient of variation was better than 6% for clozapine and norclozapine at therapeutic concentrations. Based on a plasma sample volume of 200 microliters, the limit of accurate quantitation of both clozapine and norclozapine was approximately 25 micrograms/L (coefficients of variation = 11.4% and 8.4%, respectively). The method has been used over the past 2 years for single-dose pharmacokinetic studies and for monitoring patients receiving clozapine therapy.
Freeman
D J
DJ
Robarts Research Institute, London, Ontario, Canada.
Li
M C
MC
Oyewumi
K
K
D014150:Antipsychotic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003024:Clozapine / Q000031:analogs & derivatives* / Q000097:blood* / Q000302:isolation & purification; D004347:Drug Interactions; D016903:Drug Monitoring; D006801:Humans; D018967:Risperidone / Q000097:blood; D014700:Verapamil / Q000097:blood
D014150:Antipsychotic Agents; C058272:norclozapine; D014700:Verapamil; D003024:Clozapine; D018967:Risperidone