Tri-chromic sustainable tools of derivative/discrete Fourier transform HPLC convoluted peaks: Application on LCZ696, an antihypertensive supramolecular complex, with its in process and degradation impurity analysis

Abstract

The aim of this manuscript is to discuss the use of chemometrics approaches in handling the response data of HPLC to sustainable analytical chemistry procedure development. This was performed on FDA approved LCZ696, an antihypertensive supramolecular complex of sacubitril (SAC) and valsartan (VAL), with the in process and degradation impurity (BMP). Structure similarity between SAC and its in process and degradation impurity (BMP) makes it difficult for their simultaneous determination and need too much time and solvent consumption for their separation. It was found that convolution of the resulting derivative curves using 8-points sin xi polynomials (discrete Fourier functions) after derivative treatment of the chromatographic response data was beneficial in handling one of the most common chromatographic problems which is overlapping of the chromatographic peaks without complete resolution, thus, reducing time of analysis and solvent consumption. The chemometric data handling succeeded in analyzing LCZ696, with its closely related in process impurity in less than 4.5 min. reaching impurity detection limit of 0.5 % in presence of the parent drug, SAC, while the direct chromatographic measurement showed higher LOD and LOQ of BMP with poor recovery, outside the accepted range 98–102 %, ranging from 80.56 to 104.41. Moreover, the proposed chemometric methodology will be compared with other chromatographic methods in terms of greenness, blueness and whiteness (tri-chromic assessment) using Analytical Eco Scale, AGREE, Blue Applicability Grade Index (BAGI) and the up-to-date Chlortox scale in addition to the white RGB 12 model in order to ascertain the influence of chemometric methods in minimizing the amount of time spent conducting the analysis and reducing solvent, energy and waste consumption.