Multicomponent antihypertensive pharmaceuticals determination with related impurity analysis using MEKC: Whiteness and greenness assessment

Abstract

In the present study, a white and green micellar electrokinetic chromatography method (MEKC) coupled with a photo diode array detector (DAD) has been established for challenging multi-component analysis of two antihypertensive combinations therapy. The first one is the supramolecular complex LCZ696 of valsartan (VAL) and sacubitril (SAC) with sacubitril related impurity (BMP) and the second combination is nebivolol (NEB) with thiazide like diuretics: hydrochlorothiazide (HCZ) and indapamide (IND). Separation was done using fused silica capillary (40 cm × 50 μm id) along with 10 mM phosphate buffer adjusted to pH 10 in presence of 25 mM sodium dodecyl sulphate (SDS). Linearity was assessed in the concentration ranges of 10–300, 10–300, and 5–50 μg. mL−1 for VAL, SAC, and BMP (Mix I) respectively, while for Mix II 20–200 μg. mL−1 for HCZ, IND and NEB with r > 0.9991. LOD were 3.12,3.11 and1.53 μg. mL−1for VAL, SAC, and BMP respectively. In addition, LOD for Mix II were 5.92,4.44 and 5.30 μg. mL−1for HCZ, IND and NEB respectively. The applicability of the suggested method was proved by investigating the five antihypertensive drugs at various concentrations levels in different pharmaceutical preparations with sacubitril related impurity analysis,BMP,at minute level in presence of parent drug, SAC, reaching 1.6%. Moreover, the proposed method did not rely only on the greenness evaluation tool using the most widely used Analytical Eco-Scale and the novel AGREE tool but also was merged with whiteness appraisal using RGB 12 algorithm.