title: Development and validation of an HPLC-UV method for the simultaneous determination of the antipsychotics clozapine, olanzapine and quetiapine, several beta-blockers and their metabolites.
abstract: A simple, accurate and selective column-switching high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous quantification of six beta-blockers (metoprolol, timolol, bisoprolol, propranolol, carvedilol and nebivolol), three of their metabolites (α-hydroxy metoprolol, N-desisopropyl propranolol and 4'-hydroxy carvedilol 4-HCAR), three antipsychotics (olanzapine, clozapine and quetiapine) and three of their metabolites (N-desmethyl olanzapine, N-desmethyl clozapine and N-desalkyl quetiapine) in human serum. After pretreatment on a Merck LiChrospher RP-4 ADS column (25 μm), drugs were separated on a Phenomenex Gemini Phenyl Hexyl 110 A column (250 × 4.6 mm, 5 μm) using a gradient mixture of acetonitrile and potassium dihydrogen phosphate buffer pH 3.1 (containing 10% methanol) as a mobile phase at a flow rate of 1 mL/min. The total analysis time was 40 min. For detection of the analytes, four different UV wavelengths were used: 215, 226, 242 and 299 nm. The method was validated according to the guidelines of the Society of Toxicology and Forensic Chemistry in terms of selectivity, linearity, accuracy, precision and stability and successfully applied for the analysis of the 15 described analytes in human serum.
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Margarete
authors.identifier: http://orcid.org/0000-0003-4580-9367
authors.initials: M
authors.lastname: Silva Gracia
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Köppl
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Unholzer
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Haen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000737:chemistry; D014150:Antipsychotic Agents / Q000097:blood* / Q000737:chemistry; D001569:Benzodiazepines / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D000069348:Quetiapine Fumarate / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results
chemical_list: D000319:Adrenergic beta-Antagonists; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate
keywords: HPLC; antipsychotics; beta-blockers; column-switching; therapeutic drug monitoring