title: Simultaneous Determination of Metformin, Metoprolol and its Metabolites in Rat Plasma by LC-MS-MS: Application to Pharmacokinetic Interaction Study.
abstract: A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the simultaneous quantitation of metformin (MTF), metoprolol (MET), α-hydroxymetoprolol (HMT) and O-desmethylmetoprolol (DMT) in rat plasma using paracetamol as an internal standard (IS), respectively. The sample preparation involved a protein-precipitation method with methanol after the addition of IS. The separation was performed on an Agilent HC-C18 column (4.6 × 250 mm, 5 µm) at a flow rate of 1.0 mL/min, using methanol-water containing 0.1% formic acid (39:61, v/v) as mobile phase, and total run time was 8.5 min. MS-MS detection was accomplished in multiple reaction monitoring mode with positive electrospray ionization. The monitored transitions were m/z 130.1 → 60.2 for MTF, m/z 268.2 → 116.1 for MET, m/z 284.2 → 116.1 for HMT, m/z 254.2 → 116.1 for DMT and m/z 152.3 → 110.1 for IS. The method was fully validated in terms of selectivity, linearity, accuracy, precision, stability, matrix effect and recovery over a concentration range of 19.53-40,000 ng/mL for MTF, 3.42-7,000 ng/mL for MET, 2.05-4,200 ng/mL for HMT and 1.95-4,000 ng/mL for DMT, respectively. The analytical method was successfully applied to drug interaction study of MTF and MET after oral administration of MTF and MET. Results suggested that the coadministration of MTF and MET results in a significant drug interaction in rat.
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: 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: A-xi
authors.initials: AX
authors.lastname: Shi
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, Qing Hai Provincial Hospital, Xining 810000, 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 School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xin-dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Yong-wen
authors.initials: YW
authors.lastname: Jin
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.
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: Fan
authors.initials: F
authors.lastname: Zhang
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 xinanwu6511@163.com.
authors.forename: Xin-an
authors.initials: XA
authors.lastname: Wu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D007004:Hypoglycemic Agents / Q000097:blood* / Q000493:pharmacokinetics; D057230:Limit of Detection; D008297:Male; D008687:Metformin / Q000097:blood* / Q000493:pharmacokinetics; D008790:Metoprolol / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000319:Adrenergic beta-Antagonists; D007004:Hypoglycemic Agents; D008687:Metformin; D008790:Metoprolol