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.
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.
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Shinji
S
Kobuchi
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Megumi
M
Matsuno
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Etsuko
E
Fukuda
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Yukako
Y
Ito
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. Electronic address: sakaedat@mb.kyoto-phu.ac.jp.
Toshiyuki
T
Sakaeda
D000818:Animals; D001559:Benzhydryl Compounds / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005960:Glucosides / Q000097:blood*; D007004:Hypoglycemic Agents / Q000097:blood*; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
Antidiabetic agent; LC–MS/MS; Rat plasma; Tofogliflozin