title: Fast simultaneous LC/MS/MS determination of 10 active compounds in human serum for therapeutic drug monitoring in psychiatric medication.
abstract: A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro-aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25-1000 ng/mL for agomelatine; 0.25-100 ng/mL for asenapine and iloperidone; 2.5-1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3-924.6 ng/mL for dehydroaripiprazole; 2.2-878.4 ng/mL for melperone; and 2.2-883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra-run precision of 0.4-5.5 %, inter-run precision of 0.6-8.2% and overall recovery of 87.9-114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital.
authors.affiliation: Department of Clinical Pharmacology, Department of Laboratory Diagnostics, University Hospital Ostrava, Czech Republic.|Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 779 00, Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Sistik
authors.affiliation: Department of Clinical Pharmacology, Department of Laboratory Diagnostics, University Hospital Ostrava, Czech Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Urinovska
authors.affiliation: Department of Clinical Pharmacology, Department of Laboratory Diagnostics, University Hospital Ostrava, Czech Republic.|Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava.
authors.forename: Hana
authors.initials: H
authors.lastname: Brozmanova
authors.affiliation: Department of Clinical Pharmacology, Department of Laboratory Diagnostics, University Hospital Ostrava, Czech Republic.|Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava.
authors.forename: Ivana
authors.initials: I
authors.lastname: Kacirova
authors.affiliation: Department of Psychiatry, University Hospital Ostrava, 708 52, Ostrava, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Silhan
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 779 00, Olomouc, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Lemr
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D011619:Psychotropic Drugs / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D011619:Psychotropic Drugs
keywords: mass spectrometry; psychotropic drugs; therapeutic drug monitoring