Automated Analysis of Clozapine and Norclozapine in Human Plasma Using Novel Extraction Plate Technology and Flow-Injection Tandem Mass Spectrometry

Therapeutic Drug Monitoring
Lewis CouchmanRobert J Flanagan

Abstract

Analysis of plasma clozapine and N-desmethylclozapine (norclozapine) for therapeutic drug monitoring purposes is well established. To minimize analysis times and facilitate rapid reporting of results, we have fully automated sample preparation using novel AC Extraction Plates and a Tecan Freedom EVO 100 liquid handling platform, and minimized extract analysis times using flow-injection tandem mass spectrometry (FIA-MS/MS). Analytes and deuterium-labeled internal standards were extracted from plasma (100 μL) at pH 10.6 and extracts analyzed directly using tandem mass spectrometry [20 μL injection, 0.7 mL/min methanol carrier flow, analysis time (injection-to-injection) approximately 60 seconds]. Validation data showed excellent intraplate and interplate accuracy (95%-104% nominal concentrations). Interbatch precision (% RSD) at the limit of quantitation (0.01 mg/L) was 3.5% and 5.5% for clozapine and norclozapine, respectively. Matrix effects were observed for both clozapine and norclozapine, but were compensated for by the internal standards. Overall process efficiency was 56%-70% and 66%-77% for clozapine and norclozapine, respectively. Mean relative process efficiency was 98% and 99% for clozapine and norclozapine, respective...Continue Reading

References

Aug 18, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Kateřina MičováTomáš Adam
Dec 15, 2010·Biomedical Chromatography : BMC·Lewis Couchman, Phillip E Morgan
Feb 18, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·David M S McHughWendy M Zakowicz
Dec 5, 2012·Annals of Nutrition & Metabolism·Mareile NiesserWolfgang Peissner
Mar 13, 2013·Forensic Science International : Synergy·Danielle S FisherRobert J Flanagan
Apr 11, 2013·Forensic Science International : Synergy·Danielle S FisherRobert J Flanagan

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