title: Development of a LC-MS/MS method for simultaneous determination of metoprolol and its metabolites, α-hydroxymetoprolol and O-desmethylmetoprolol, in rat plasma: application to the herb-drug interaction study of metoprolol and breviscapine.
abstract: A simple, specific and sensitive LC-MS/MS method was developed and validated for the simultaneous determination of metoprolol (MET), α-hydroxymetoprolol (HMT) and O-desmethylmetoprolol (DMT) in rat plasma. The plasma samples were prepared by protein precipitation, then the separation of the analytes was performed on an Agilent HC-C18 column (4.6 × 250 mm, 5 µm) at a flow rate of 1.0 mL/min, and post-column splitting (1:4) was used to give optimal interface flow rates (0.2 mL/min) for MS detection; the total run time was 8.5 min. Mass spectrometric detection was achieved using a triple-quadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. The method was fully validated in terms of selectivity, linearity, accuracy, precision, stability, matrix effect and recovery over a concentration range of 3.42-7000 ng/mL for MET, 2.05-4200 ng/mL for HMT and 1.95-4000 ng/mL for DMT. The analytical method was successfully applied to herb-drug interaction study of MET and breviscapine after administration of breviscapine (12.5 mg/kg) and MET (40 mg/kg). The results suggested that breviscapine have negligible effect on pharmacokinetics of MET in rats; the information may be beneficial for the application of breviscapine in combination with MET in clinical therapy.
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Rao
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.|School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Yan-rong
authors.initials: YR
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Qin
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.|School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.|Department of Pharmacy, Qinhai Provincial Hospital, Xining, 810007, China.
authors.forename: Ya-feng
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.
authors.forename: Yu-hui
authors.initials: YH
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.
authors.forename: Guo-qiang
authors.initials: GQ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.|School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Xing-dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou, 730000, China.
authors.forename: Xin-an
authors.initials: XA
authors.lastname: Wu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000032:analysis* / Q000493:pharmacokinetics; D005419:Flavonoids / Q000097:blood* / Q000493:pharmacokinetics; D041743:Herb-Drug Interactions; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C061097:breviscapine; C029504:alpha-hydroxymetoprolol; D008790:Metoprolol
keywords: LC-MS/MS; herb-drug interaction; metabolites; metoprolol; pharmacokinetics