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  2. 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

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

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Sep 1;1000:22-8. doi: 10.1016/j.jchromb.2015.07.013.
Shinji Kobuchi 1 Yukako Ito 1 Kyoka Yano 1 Toshiyuki Sakaeda 2
Affiliations

Affiliations

  • 1 Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
  • 2 Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. Electronic address: sakaedat@mb.kyoto-phu.ac.jp.
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.

Keywords

Empagliflozin; Ipragliflozin; Liquid chromatography-tandem mass spectrometry; SGLT2.

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