A Multivariate Curve Resolution Approach to the Study of the Degradation Kinetics of Valsartan under Photolytic and Acid Conditions

Abstract

The analysis of UV‐spectrophotometric data with second‐order chemometrics techniques, including multivariate curve resolution with alternating least‐squares (MCR‐ALS) and hybrid hard‐ and soft MCR (HS‐MCR), was examined as an alternative tool for studying the kinetics of drug degradation under stress conditions, employing valsartan (VAL) as a model drug. Despite small structural and spectroscopic differences between VAL and its degradation products, MCR‐ALS and HS‐MCR were able to detect the generation of two photoneutral degradation products (DP‐1 and DP‐2) and a single acid hydrolysis product (DP‐3), providing good approximations to their pure spectra and concentration profiles, from which estimations of the kinetic profiles and rate constants were obtained. Kinetic models based on first‐order reactions explained the degradation processes. MCR‐ALS and HS‐MCR analyses yielded similar rate constants; however, the latter was capable of more properly fitting the experimental data to a kinetic model in the case of drug photolysis. The results were confirmed by comparison with data obtained by HPLC analysis of the degraded samples.

Comparative Study of Hard- and Soft-Modeling Algorithms for Kinetic Data Processing

“…The use of HM‐ALS methodology to analyze simple first‐order kinetics has been described in the literature . In the current work, the algorithm has been generalized to analyze mechanisms of any complexity.…”