A simple and rapid LC-MS/MS method for quantitation of luseogliflozin in rat plasma and its application to a PK study.

AIM: Luseogliflozin is a novel sodium-dependent glucose cotransporter-2 inhibitor for the treatment of Type 2 diabetes mellitus. To assist pharmacokinetic and toxicodynamic studies, a rapid LC-MS/MS method were developed and validated for the quantitation of luseogliflozin in rat plasma. RESULTS: Sample preparation was carried out using simplified protein precipitation and liquid-liquid extraction procedures, and the run time was only 4 min. Extraction recovery was 92.9 to 95.3%, and the method was validated over the range 0.5 to 500 ng/ml for luseogliflozin with acceptable specificity, accuracy and precision. CONCLUSION: The validated method is considered suitable to quantify luseogliflozin in pharmacokinetic and pharmacodynamic/toxicodynamic studies 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.

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.