Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Canagliflozin and Metformin HCl in Rat Plasma and its Application

Background: Food and herbal extracts rich in Quercetin (QRT) are often self-medicated by diabetics and can potentially alter the pharmacokinetics (PK) of Metformin HCl (MET) and Canagliflozin (CNG) leading to food or herb-drug interactions and reduced therapeutic efficacy. However, the impact of these flavonoids on the pharmacokinetic behaviour of MET and CNG is mostly unknown. Methods: A simple one-step protein precipitation method was developed for the determination of MET and CNG from rat plasma. The mobile phase chosen was MeOH 65% and 35% water containing 0.1% formic acid at a flow rate of 1mL/min. Results: The retention time of MET, internal standard (Valsartan) and CNG was 1.83, 6.2 and 8.2 min, respectively. The method was found to be linear in the range of 200 - 8000 ng/mL for CNG and 100 = 4000 ng/ml for MET. Precision and accuracy of the method were below 20% at LLOQ and below 15% for LQC, MQC, and HQC. Conclusion: The method was successfully applied for the determination of PK of MET and CNG by using 100 μL of rat plasma. QRT co-administration affects the PK parameters of MET and CNG. This alteration in PK parameters might be of significant use for clinicians and patients.