Central composite design as an analytical optimization tool for the development of eco-friendly HPLC-PDA methods for two antihypertensive mixtures containing the angiotensin receptor blocker Valsartan: Greenness assessment by four evaluation tools

Abstract

Using green chemistry principles in chromatography has grown tremendously in recent years. Two green HPLC techniques for determining two antihypertensive binary mixtures, (Nebivolol hydrochloride/Valsartan mixture) and (Sacubitril/Valsartan mixture), were developed and validated. Green Analytical Chemistry (GAC) principles were used, with the employed solvents and analysis run time having a significant impact on the method's greenness. In the mobile phase, the organic modifier was “non-toxic” ethanol. The two-factor three-level response surface methodology was used to optimize analyte separation in both mixtures in a short time span. For the first mixture, phosphate buffer (pH 3): ethanol (21:79 v/v) was used as the mobile phase, where the separation time was 2.5 min. On the other hand, the second mixture was separated using phosphate buffer (pH 3): ethanol (35:65 v/v) in 6 min. It is worth mentioning that using green solvents did not affect the resolution, which was 10.1 and 3.1 for the first and second mixtures, respectively. Four well-known GAC evaluation techniques were used to assess the greenness of the proposed methods on a qualitative and quantitative level: The National Environmental Methods Index (NEMI), analytical eco-scale, Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE). The proposed methods were statistically compared to other published chromatographic methods, and no significant differences in accuracy were discovered. Meanwhile, there is a major variation in the approaches' greenness. The suggested procedures proved to be an excellent, environmentally friendly alternative to the previously mentioned approaches.