Implementation of white analytical chemistry-driven analytical quality risk assessment and design of experiments to multipurpose chromatographic method for the synchronous estimation of multiple drugs co-formulated with paracetamol

Abstract

In the pharmaceutical industry, several fixed-dose paracetamol combinations have been manufactured and marketed. Several chromatographic methods have been documented in the literature for the quality control of these fixed-dose combinations (FDCs). Yet, these chromatographic procedures were developed using teratogenic and neurotoxic organic solvents that are harmful to the environment and dangerous to human and animal life. As a result, a multipurpose chromatographic technique was developed combining principles of white analytical chemistry, quality risk assessment, and experimental design. To reduce the time and cost of analysis, this chromatographic method needs a single chromatographic condition for the quality control of multiple FDCs of paracetamol. To safeguard the environment and human life, the suggested chromatographic process employs low-toxicity possible solvents. The analytical quality risk assessment methodology by Placket‒Burman design was used to identify significant analytical method risk parameters and analytical quality attributes. Response surface analysis by mixture design was used to optimize the identified critical method risk parameters. Using unique principles of white analytical chemistry, the proposed and published chromatographic techniques were assessed for their validation efficiency, greenness profile, time efficiency, and cost efficiency for the estimation of FDCs of paracetamol with multiple drugs.