Innovative spectrophotometric methods for simultaneous estimation of the novel two-drug combination: Sacubitril/Valsartan through two manipulation approaches and a comparative statistical study

Different innovative spectrophotometric methods were introduced for the first time for simultaneous quantification of sacubitril/valsartan in their binary mixture and in their combined dosage form without prior separation through two manipulation approaches. These approaches were developed and based either on two wavelength selection in zero-order absorption spectra namely; dual wavelength method (DWL) at 226 nm and 275 nm for valsartan, induced dual wavelength method (IDW) at 226 nm and 254 nm for sacubitril and advanced absorbance subtraction (AAS) based on their iso-absorptive point at 246 nm (lambda(iso)) and 261 nm (sacubitril shows equal absorbance values at the two selected wavelengths) or on ratio spectra using their normalized spectra namely; ratio difference spectrophotometric method (RD) at 225 nm and 264 nm for both of them in their ratio spectra, first derivative of ratio spectra (DR1) at 232 nm for valsartan and 239 nm for sacubitril and mean centering of ratio spectra (MCR) at 260 nm for both of them. Both sacubitril and valsartan showed linearity upon application of these methods in the range of 2.5-25.0 mu g/mL. The developed spectrophotmetric methods were successfully applied to the analysis of their combined tablet dosage form ENTRESTO (TM). The adopted spectrophotometric methods were also validated according to ICH guidelines. The results obtained from the proposed methods were statistically compared to a reported HPLC method using Student t-test, F-test and a comparative study was also developed with one-way ANOVA, showing no statistical difference in accordance to precision and accuracy. (C) 2017 Elsevier B.V. All rights reserved.