Development and Validation of Spectrophotometric Methods for the Determination of Canagliflozin or Gliclazide and Metformin in the Presence of Metformin Impurity (1-Cyanoguanidine).

Quantitative multicomponent analysis is considered an analytical goal to save time and cost in analysis. This work aimed to provide sensitive and selective [successive ratio subtraction coupled with constant multiplication (SRS-CM) and chemometric] methods for the determination of coformulated antidiabetic drugs, namely canagliflozine and metformin or gliclazide and metformin in presence of metformin degradation product, 1-cyanoguanidine. SRS-CM method was developed for the determination of canagliflozin and metformin at 292 and 237 nm, respectively, using 14 μg/mL canagliflozin as a divisor in the first step to cancel the spectrum of canagliflozin. Then, 18 μg/mL metformin was used as a divisor in the second step to cancel the spectrum of metformin. Finally, we obtained the spectrum of cyanoguanidine. Chemometric method was applied for the determination of the gliclazide and metformin mixture in a 225-235 nm range. Sample enrichment technique was used to increase the concentration of canagliflozin or gliclazide to allow its simultaneous determination with metformin without prior separation. Validation parameters according to the International Conference on Harmonization guidelines were satisfactory over the concentration ranges of 5 to 16 μg/mL for canagliflozin and metformin as well as 2.5 to 12.5 and 6 to 24 μg/mL for gliclazide and metformin, respectively. The method provides sufficient selectivity and accuracy to be applied for routine analysis and quality control in laboratories for the cited drugs. This work shows two examples to how to select a suitable UV spectrophotometric method to overcome the spectral overlap.