Resolving Problems Encountered in Spectrophotometric Analysis of a Ternary Mixture of Linagliptin, Empagliflozin and Metformin Hydrochloride

Abstract There are two main problems encountered in spectrophotometric analysis of a ternary mixture composed of linagliptin LINA, empagliflozin EMPA and metformin hydrochloride MET. The first problem is due to the severe overlap in their zero and derivative spectra. To overcome this problem, LINA was determined by direct spectrophotometry at λ max = 298 nm where there is no interference from other components while, EMPA and MET were determined using double divisor ratio spectra derivative method DDRD. In this method, the first derivative spectra were calculated for ratio spectra generated by dividing the absorption spectra of ternary mixtures containing increasing concentrations of one of the components by a standard spectrum of binary mixture of the other two components (double divisor). The calibration graphs were constructed by measuring the amplitude at either the minimum or maximum wavelengths against the concentrations. The selected wavelengths for determination of EMPA and MET are 282.92 and 250 nm, respectively. The second problem arises from the presence of LINA and EMPA as minor components in their recently approved dosage form with MET thus, sample enrichment through spiking was employed for LINA and EMPA to enable their spectrophotometric analysis in laboratory prepared mixtures that have the same ratio of the three components as in their pharmaceutical dosage form. GRAPHICAL ABSTRACT