1. Academic Validation
  2. Development and validation of an LC-MS/MS method for the determination of tofogliflozin in plasma and its application to a pharmacokinetic study in rats

Development and validation of an LC-MS/MS method for the determination of tofogliflozin in plasma and its application to a pharmacokinetic study in rats

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Aug 1;1027:227-33. doi: 10.1016/j.jchromb.2016.05.053.
Shinji Kobuchi 1 Megumi Matsuno 1 Etsuko Fukuda 1 Yukako Ito 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: [email protected].
Abstract

Tofogliflozin is a novel selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) and has been developed for the treatment of patients with type 2 diabetes mellitus. In this study, a highly sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitation of tofogliflozin in rat plasma was developed and validated. The detection was performed using an API 3200 triple-quadrupole mass spectrometer with selected reaction monitoring (SRM) in the positive electrospray ionization mode. The SRM transitions were m/z=387.1 [M+H](+)→267.1 for tofogliflozin and m/z=451.2 [M+H](+)→71.0 for empagliflozin (internal standard: I.S.). Chromatographic separation was performed on a Quicksorb ODS (2.1mm i.d.×150mm, 5μm size) using isocratic elution with acetonitrile/10mM ammonium acetate (50:50, v/v) as the mobile phase at a flow rate of 0.2mL/min and the total run time was 4.0min. The lower limit of quantification (LLOQ) for tofogliflozin was 0.5ng/mL with sufficient specificity, accuracy, and precision. The validated method was successfully applied to the pharmacokinetic studies of tofogliflozin in rats. This assay method could be a valuable tool for future studies including pharmacokinetic and pharmacodynamic studies of SGLT2 inhibitors.

Keywords

Antidiabetic agent; LC–MS/MS; Rat plasma; Tofogliflozin.

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