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Simultaneous determination of metoprolol and its metabolites, α‐hydroxymetoprolol and O ‐desmethylmetoprolol, in human plasma by liquid chromatography with tandem mass spectrometry: A pplication to the pharmacokinetics of metoprolol associated with CYP 2 D 6 genotypes
Author(s) -
Bae Soo Hyeon,
Lee Joeng Kee,
Cho DooYeoun,
Bae Soo Kyung
Publication year - 2014
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201301353
Subject(s) - chemistry , chromatography , metoprolol , pharmacokinetics , analyte , formic acid , selected reaction monitoring , mass spectrometry , detection limit , liquid chromatography–mass spectrometry , coefficient of variation , tandem mass spectrometry , analytical chemistry (journal) , pharmacology , medicine , cardiology
A rapid and simple LC with MS / MS method for the simultaneous determination of metoprolol and its two CYP 2 D 6‐derived metabolites, α‐hydroxy‐ and O ‐desmethylmetoprolol, in human plasma was established. Metoprolol ( MET ), its two metabolites, and the internal standard chlorpropamide were extracted from plasma (50 μL) using ethyl acetate. Chromatographic separation was performed on a L una CN column with an isocratic mobile phase consisting of distilled water and methanol containing 0.1% formic acid (60:40, v/v) at a flow rate of 0.3 mL/min. The total run time was 3.0 min per sample. Mass spectrometric detection was conducted by ESI in positive ion selected‐reaction monitoring mode. The linear ranges of concentration for MET , α‐hydroxymetoprolol, and O ‐desmethylmetoprolol were 2–1000, 2–500, and 2–500 ng/mL, respectively, with a lower limit of quantification of 2 ng/mL for all analytes. The coefficient of variation for the assay's precision was ≤ 13.2%, and the accuracy was 89.1–110%. All analytes were stable under various storage and handling conditions and no relevant cross‐talk and matrix effect were observed. Finally, this method was successfully applied to assess the influence of CYP2D6 genotypes on the pharmacokinetics of MET after oral administration of 100 mg to healthy K orean volunteers.