title: Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.
abstract: A liquid chromatographic/mass spectrometric assay with atmospheric pressure chemical ionization (APCI-LC/MS) is presented for the fast and reliable screening and identification and for the precise and sensitive quantification of 15 neuroleptic (antipsychotic) drugs and three of their relevant metabolites in plasma. It allows confirmation of the diagnosis of a neuroleptic overdose and monitoring of psychiatric patients' compliance. The neuroleptics amisulpride, bromperidol, clozapine, droperidol, flupenthixol, fluphenazine, haloperidol, melperone, olanzapine, perazine, pimozide, risperidone, sulpiride, zotepine and zuclopenthixol and the pharmacologically active metabolites norclozapine, clozapine N-oxide and 9-hydroxyrisperidone were extracted from plasma using solid-phase extraction and were separated on a Merck LiChroCART column with Superspher 60 RP Select B as the stationary phase. Gradient elution was performed using aqueous ammonium formate and acetonitrile. After screening and identification in the scan mode using the authors' new LC/MS library, the neuroleptics were quantified in the selected-ion mode. The quantification assay was fully validated. It was found to be selective and proved to be linear from sub-therapeutic to over therapeutic concentrations for all analytes. The corresponding reference levels are listed. The accuracy and precision data were within the required limits. The analytes were stable in frozen plasma for at least 1 month. The method was successfully applied to several authentic plasma samples from patients treated or intoxicated with various neuroleptics. The validated LC/MS assay has proved to be appropriate for the isolation, separation, screening, identification and quantification of various neuroleptics in plasma for clinical toxicology and therapeutic drug monitoring purposes.
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Saarland, D-66421 Homburg (Saar), Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kratzsch
authors.forename: Frank T
authors.initials: FT
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraemer
authors.forename: Armin A
authors.initials: AA
authors.lastname: Weber
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D001274:Atmospheric Pressure; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D006801:Humans; D007477:Ions; D013058:Mass Spectrometry; D015394:Molecular Structure; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014150:Antipsychotic Agents; D007477:Ions