A validated high-resolution accurate mass LC-MS assay for quantitative determination of metoprolol and α-hydroxymetoprolol in human serum for application in pharmacokinetics

• Main Authors: Sjoukje Postma-Kunnen, Jan Peter Yska, Gerard Hommema, Sikke Koopmans, Bob Wilffert, Eric N. van Roon
• Format: Article
• Language: English
• Published: Betasciencepress Publishers 2017-06-01
• Series: Journal of Applied Bioanalysis
• Subjects: metoprolol; α-hydroxymetoprolol; LC-MS; orbitrap mass spectrometer; pharmacokinetics.
• Online Access: https://doi.org/10.17145/jab.17.008

To determine metoprolol and its metabolite α-hydroxymetoprolol in human serum we validated a method on an LC system with an Exactive® Orbitrap mass spectrometer (Thermo Scientific) as detector and isotope-labelled metoprolol-d7 as internal standard. A simple sample preparation was used with water-acetonitrile (15:85, v/v) as precipitation reagent. This method has a chromatographic run time of 15 min and linear calibration curves in the range of 5.0-250 μg/L for both metoprolol and α-hydroxymetoprolol. Validation showed the method to be accurate, with a good precision, selective and with a lower limit of quantitation of 2.0 μg/L for metoprolol and 1.0 μg/L for α-hydroxymetoprolol, respectively. This validated LC-Orbitrap MS analysis for metoprolol and α-hydroxymetoprolol can be used for application in human pharmacokinetics.