Stability indicating RP-HPLC and spectrophotometric methods for determination of gliflozins in their mixture with metformin

Abstract

Metformin hydrochloride is the only biguanide that used alone or in combination with other antidiabetic drugs such as one of the following gliflozins; empagliflozin (EMPA), dapagliflozin (DAPA), or canagliflozin (CANA) to control type 2 diabetes mellitus. The developed HPLC method can determine MET, EMPA, DAPA and CANA simultaneously in presence of metformin complete oxidation degradation product. It is the first stability indicating method for the determination of this mixture. The separation is Isocratic RP-HPLC at 260 nm using Acetonitrile and 0.1% Ortho phosphoric acid (65:35v/v) as a mobile phase which is pumped with a flow rate 1.0 ml/min to a Kromasil C18 analytical column (250 mm, 4.6 mm, 5 μm). Also MET has been determined in its ternary mixture with EMPA and CANA, were MET and EMPA determined by Mean centering of ratio spectra (MCR) method at peak amplitude 236.8 nm and 228.6 nm, respectively, while CANA is directly determined at λ max 290 nm. The methods are validated according to ICH guidelines, and the results were statistically compared with the reported methods.