title: Development and validation of a multi-analyte LC-MS/MS approach for quantification of neuroleptics in whole blood, plasma, and serum.
abstract: Based on a similar approach for quantification of antidepressants, benzodiazepines, and z-drugs, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) multi-analyte approach with simple liquid-liquid extraction was extended for fast target screening and quantification of neuroleptics in whole blood, plasma, and serum. As this method is part of a multi-analyte procedure for over 100 analytes from different drug classes and as the extracts were additionally used in the authors' laboratory for gas chromatography-mass spectrometry (GC-MS) analysis, one universal stable-isotope-labelled internal standard (SIL-IS) was used to save time and resource. The method was validated with respect to international guidelines. For accuracy and precision, full calibration was performed with ranges from subtherapeutic to toxic concentrations. Selectivity problems could not be observed, but matrix effects ranged from 68 to 211% in all samples. For the low quality control (QC), recovery ranged from 32 to 112%, process efficiency from 31 to 165% and for the high QC recovery from 42 to 141%, process efficiency from 29 to 154%. In addition statistical data evaluation of the variances of the recovery, matrix effects, and process efficiency data between whole blood vs. plasma, whole blood vs. serum, and plasma vs. serum were done. The presented LC-MS/MS approach was applicable for selective detection of 33 neuroleptics as well as accurate and precise quantification of 25 neuroleptics in whole blood, 19 in plasma, and 17 in serum. More significant matrix effects (ME) for neuropletic drugs overall in plasma and serum as compared with whole blood were detected. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Institute of Legal Medicine, Saarland University, Kirrberger Straße Building 42, 66421, Homburg (Saar), Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Montenarh
authors.affiliation: Institute of Legal Medicine, Saarland University, Kirrberger Straße Building 42, 66421, Homburg (Saar), Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hopf
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, D-66421, Homburg (Saar), Germany.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
authors.affiliation: Institute of Legal Medicine, Saarland University, Kirrberger Straße Building 42, 66421, Homburg (Saar), Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schmidt
authors.affiliation: Institute of Legal Medicine, Saarland University, Kirrberger Straße Building 42, 66421, Homburg (Saar), Germany. andreas.ewald@uks.eu.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Ewald
mesh_terms: D000928:Antidepressive Agents / Q000032:analysis* / Q000737:chemistry*; D014150:Antipsychotic Agents / Q000097:blood; D001569:Benzodiazepines / Q000032:analysis* / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D010949:Plasma / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines
keywords: LC-MS/MS; matrix effects; neuroleptics; validation