title: A quantitative LC-MS/MS method for determining ipragliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, and its application to a pharmacokinetic study in rats.
abstract: Ipragliflozin is a highly potent and selective sodium-dependent glucose co-transporter-2 (SGLT2) inhibitor, a novel class of hypoglycemic agents. The aim of the present study was to establish a new highly sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of ipragliflozin in rat plasma and apply this method to a pharmacokinetic study in rats. Empagliflozin was used as an internal standard (I.S.) and liquid-liquid extraction was conducted using tert-butyl methyl ether. Chromatographic separation was accomplished on a Quicksorb ODS (2.1mm i.d.×150mm, 5μm in size) with acetonitrile/0.1% formic acid (90:10, v/v) at a flow rate of 0.2mL/min. An API 3200 triple quadrupole mass spectrometer operating in the positive electrospray ionization mode with multiple reaction monitoring was used to detect ipragliflozin and I.S. transitions: m/z 422.0 [M+NH4](+)→151.0 for ipragliflozin and m/z 451.2 [M+H](+)→71.0 for I.S. Inter- and intra-day accuracies and precisions were within ±15%. This validated method was successfully applied to a pharmacokinetic study of ipragliflozin in rats. This assay method may contribute to assessment of novel SGLT2 inhibitors using the rat as an animal model.
authors.affiliation: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kobuchi
authors.affiliation: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Kyoka
authors.initials: K
authors.lastname: Yano
authors.affiliation: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. Electronic address: sakaedat@mb.kyoto-phu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005960:Glucosides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013876:Thiophenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D005960:Glucosides; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C572941:ipragliflozin
keywords: Empagliflozin; Ipragliflozin; Liquid chromatography-tandem mass spectrometry; SGLT2