Ultra-fast LC-MS/MS in therapeutic drug monitoring: Quantification of clozapine and norclozapine in human plasma.
A novel approach to high-throughput, targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has been developed. A single chromatographic system can be used for the analysis of a range of 20 drugs and metabolites with a total analysis time of 36 s (one 96-well plate of prepared samples per hour). To demonstrate the applicability of this approach to quantitative analysis, a method has been validated for the therapeutic drug monitoring of clozapine and norclozapine following automated extraction from human plasma. Chromatographic retention times were 11.4 and 12.4 s for norclozapine and clozapine, respectively (for both analytes the chromatographic peak width was less than 1 s). Comparison with a conventional LC-MS/MS method (5 min analysis time) showed excellent agreement. This new approach offers analysis times more akin to flow-injection analysis, but is likely to be more widely applicable because of chromatographic resolution from residual matrix components and isobaric interferences.
['Couchman|Lewis|L|http://orcid.org/0000-0002-0464-7886', 'Fisher|Danielle S|DS|', 'Subramaniam|Krithika|K|', 'Handley|Simon A|SA|', 'Boughtflower|Robert J|RJ|', 'Benton|Christopher M|CM|', 'Flanagan|Robert J|RJ|']
D014150:Antipsychotic Agents D002853:Chromatography, Liquid D003024:Clozapine D016903:Drug Monitoring D006801:Humans D010949:Plasma D015203:Reproducibility of Results
LC-MS/MS clozapine high-throughput mass spectrometry TDM liquid chromatography