A novel approach to quantitative LC-MS/MS: therapeutic drug monitoring of clozapine and norclozapine using isotopic internal calibration

Therapeutic drug monitoring (TDM) requires timely results in order to be clinically helpful. Such assays, when carried out using mass spectrometry-based methods, typically involve a batched sample approach with multipoint calibration. Isotopic internal calibration offers the possibility of open-acce...

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Bibliographic Details
Published in:Analytical and bioanalytical chemistry 2013-11, Vol.405 (29), p.9455-9466
Main Authors: Couchman, Lewis, Belsey, Sarah L., Handley, Simon A., Flanagan, Robert J.
Format: Article
Language:English
Subjects:
Analysis
Analytical Chemistry
Antipsychotic Agents - blood
Antipsychotic Agents - therapeutic use
Biochemistry
Calibration
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Chromatography
Chromatography, High Pressure Liquid - methods
Chromatography, High Pressure Liquid - standards
Clozapine
Clozapine - analogs & derivatives
Clozapine - blood
Clozapine - therapeutic use
Complications and side effects
Deuterium - chemistry
Drug Monitoring - methods
Drug Therapy
Drugs
Food Science
Health aspects
Humans
Hydrochloric acid
Isotope Labeling
Laboratory Medicine
Mass spectrometry
Mathematical analysis
Methods
Monitoring
Monitoring/Environmental Analysis
Patients
Quality assessment
Research Paper
Scientific imaging
Spectroscopy
Tandem Mass Spectrometry - methods
Tandem Mass Spectrometry - standards
Therapeutic drug monitoring
Time division multiplexing
Toxicology
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Summary:Therapeutic drug monitoring (TDM) requires timely results in order to be clinically helpful. Such assays, when carried out using mass spectrometry-based methods, typically involve a batched sample approach with multipoint calibration. Isotopic internal calibration offers the possibility of open-access mass spectrometric analysis with consequent shortening of turnaround times. We measured plasma clozapine and N -desmethylclozapine (norclozapine) concentrations in (1) external quality assessment (EQA) samples ( N  = 22) and (2) patient samples ( N  = 100) using liquid chromatography-tandem mass spectrometry with isotopic internal calibration (ICAL-LC-MS/MS). Analyte concentrations were calculated from graphs of the response of three internal calibrators (clozapine-D 4 , norclozapine-D 8 , and clozapine-D 8 ) against concentration. Precision (% RSD) and accuracy (% nominal concentrations) for the ICAL-LC-MS/MS method were
ISSN:1618-2642
1618-2650
DOI:10.1007/s00216-013-7361-8