A validated LC‐MS/MS method for the determination of canagliflozin, a sodium–glucose co‐transporter 2 (SGLT‐2) inhibitor, in a lower volume of rat plasma: application to pharmacokinetic studies in rats

Abstract

Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of canagliflozin in a lower volume of rat plasma (0.1 mL) was established and applied to a pharmacokinetic study in rats. Following liquid-liquid extraction by tert-butyl methyl ether, chromatographic separation of canagliflozin was performed on a Quicksorb ODS (2.1 mm i.d. × 150 mm, 5 µm size) using acetonitrile-0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.2 mL/min. The detection was carried out using an API 3200 triple-quadrupole mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z = 462.0 [M + NH4 ](+) → 191.0 for canagliflozin and m/z = 451.2 [M + H](+) → 71.0 for empagliflozin (internal standard) were obtained. The validation of the method was investigated, and it was found to be of sufficient specificity, accuracy and precision. Canagliflozin in rat plasma was stable under the analytical conditions used. This validated method was successfully applied to assess the pharmacokinetics of canagliflozin in rats using 0.1 mL rat plasma. Copyright © 2016 John Wiley & Sons, Ltd.

A fast and accurate isotope dilution GC‐IT‐MS/MS method for determination of eugenol in different tissues of fish: Application to a depletion study in mandarin fish

“…The absolute matrix factors (MFs) for QC samples were assessed by comparing the peak area of the QC samples fortified in acetonitrile with those in the supernatant of the extracted blank fish tissues. The IS normalized MFs were evaluated by comparing the peak area ratio of eugenol to IS fortified in acetonitrile with those in the supernatant of the extracted blank fish tissues (Kobuchi, Yano, Ito, & Sakaeda, ).…”

Analytical tools for determination of new oral antidiabetic drugs, glitazones, gliptins, gliflozins and glinides, in bulk materials, pharmaceuticals and biological samples

“…The following antidiabetics were measured in plasma: PIO [117,118,143,144,151] and ROS [148] (Table 11), SIT [25,142,145,147], SAX [131], VIL [123] (Table 12), DAP [146], CAN [124,135], IPR [136] (Table 13), MIT [137,150], REP [125,138,139,152] and NAT [126,140] (Table 14). The parent drugs in the presence of their metabolites were frequently determined.…”

“…The LC-MS/MS methods are mainly based on positive ESI with multiple reaction monitoring (MRM) [122,136,137,147,158,] or selected reaction monitoring (SRM) modes [127,131,135,143,156]. However, procedures involving negative ESI are also reported [124,146] as are procedures based on APCI [118] (Fig.…”

“…Also, the classic liquid-liquid extraction (LLE) with organic solvents, including ethyl acetate, tert-butyl methyl Where: CAA is p-chloranilic acid. ether (TBME), diethyl ether and dichloromethane, was frequently used [132][133][134][135][136][137][138][139][140][141].…”

A Validated Lc-MS/MS Method for Pharmacokinetic Study of Canagliflozin in Healthy Rabbits

“…As per the Literature Survey, it is revealed that the Ultraviolet spectroscopy (UV), High-Performance Liquid Chromatography (HPLC) and High-Performance thin layer Chromatography (HPTLC) methods were reported for degradation studies and to estimate the canagliflozin from bulk and Pharmaceutical dosage forms [5][6][7][8][9][10]. Ultra High Performance/liquid Chromatography-Mass Spectroscopy (UHPLC-MS and LC-MS/MS) methods were reported for quantification of the drug in biological fluids like human and rat plasma [11,12]. To best of our knowledge, no published LC-MS/MSbased methods for the pharmacokinetic study of canagliflozin in healthy rabbits.…”