title: Therapeutic drug monitoring of mirtazapine, desmethylmirtazapine, 8-hydroxymirtazapine, and mirtazapine-N-oxide by enantioselective HPLC with fluorescence detection.
abstract: The tetracyclic antidepressant mirtazapine has been in clinical use for several years as a racemic drug. Because of a relatively narrow therapeutic index, therapeutic drug monitoring may be helpful to individually optimize therapy with mirtazapine. An enantioselective high-performance liquid chromatography (HPLC) method with fluorescence detection has been developed for the quantification of mirtazapine, desmethyl mirtazapine, 8-hydroxy mirtazapine, and mirtazapine N-oxide. The method is suitable for the analysis of plasma and urine samples in the range from 1 to 100 ng/mL with precision (coefficient of variation, or CV) between 12% and 19%. The sample preparation step comprises a liquid-solid extraction procedure with good recoveries, between 85% and 99%. Patient samples for therapeutic drug monitoring as well as concentration-time series were assayed and the resulting enantiomer ratios analyzed. Typical trough levels were between 1 and 100 ng/mL, with enantiomer ratios of approximately 0.42 (S/R). In concentration-time series, enantiomer ratios distinctively greater than 1 were observed at early time points. Because the enantiomers of mirtazapine and desmethyl mirtazapine have different pharmacological properties, the method is believed to be helpful in understanding the concentration-effect relationships in the former.
authors.affiliation: Department of Clinical Pharmacology University of Goettingen, Goettingen, Germany. imeineke@med.uni-goettingen.de
authors.forename: Ingolf
authors.initials: I
authors.lastname: Meineke
authors.forename: Hannelore
authors.initials: H
authors.lastname: Steinmetz
authors.forename: Julia
authors.initials: J
authors.lastname: Kirchheiner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brockmöller
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005453:Fluorescence; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000078785:Mirtazapine; D011786:Quality Control; D013237:Stereoisomerism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D003497:Cyclic N-Oxides; C517416:desmethylmirtazapine; C517417:mirtazapine-N-oxide; D008803:Mianserin; D000078785:Mirtazapine; C415843:8-hydroxymirtazapine