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 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

“…The retention times for canagliflozin and the IS were around 1.6 min. Based on the void volume of the column and flow rate of the mobile phase in this assay, there is a possibility of a lack of chromatographic retention of canagliflozin and the IS, which is consistent with the LC-MS/MS assay method for ipragliflozin (the SGLT2 inhibitor with a C-glycoside structure and thiophene ring; Kobuchi et al, 2015). Different mobile phase pH and columns were tested; however, the current method was the most effective and sensitive for the analysis of canagliflozin in rat plasma.…”

“…The validated LC-MS/MS assay method could determine the plasma concentration of canagliflozin at 48 h after oral administration (50.8 ± 20.4 ng/mL). The noncompartmental pharmacokinetic analysis revealed that the mean elimination of canagliflozin from plasma (14.8 h) (Table 4) was slower than that of ipragliflozin (7.6 h) after oral administration of 1.0 mg/kg ipragliflozin, which was based on the clinical dosage, to rats (Kobuchi et al, 2015). These observations suggest that the validated assay method could be a valuable tool for evaluating the pharmacokinetics of canagliflozin in rats.…”

“…Although the mobile phase containing ammonium salt can effectively gain the ammonium adduct ion [M + NH 4 ] + , we could not obtain an effective and sensitive chromatographic peak of the analyte, possibly because of an insufficient chromatographic separation of the biological matrix or glucuronides in the rat plasma sample. Based on our previous study (Kobuchi et al, 2015), empagliflozin, which is an SGLT2 inhibitor, was adapted as the IS, and the transition m/ z = 451.2 → 71.0 in positive ESI detection mode was selected for its analysis. Figure 3 shows the selected ion monitoring chromatograms of canagliflozin and the IS from blank plasma, blank rat plasma spiked with canagliflozin and rat plasma obtained 1 h after oral administration of canagliflozin (2.0 mg/kg) to rats.…”

“…In the analysis of dapagliflozin, an SGLT2 inhibitor, in rat plasma by Aubry et al (2010), the matrix effect was reported to be 0.6. Moreover, we developed the LC-MS/ MS method for the quantitative analysis of ipragliflozin in rat plasma, and the mean MF ranged from 1.11 to 1.50, whereas there was no significant lot-to-lot difference in matrix effects (Kobuchi et al, 2015). Protein precipitation and liquid-liquid extraction were selected in the current study because it is the simplest, fastest, and most common practice for preparing samples in pharmacokinetic studies.…”

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“…Handful clinical trials were reported in the literature for Empagliflozin [11][12][13][14][15] . But scarcely reports have been found for RP-HPLC determination of Empagliflozin in pharmaceutical preparations.…”