Integrated Approach of White Analytical Chemistry and Analytical Quality by Design to Multipurpose RP-HPLC Method for Synchronous Estimation of Multiple Fixed-Dose Combinations of Paracetamol

BackgroundParacetamol is commonly used and manufactured over-the-counter painkiller and comes in a variety of fixed-dose combos with other medications. The RP-HPLC method is frequently used in the pharmaceutical sector for the regular analysis and quality control of these paracetamol combinations. For RP-HPLC analyses of fixed-dose combinations of paracetamol, acetonitrile and methanol are frequently used as the organic solvents of choice. However, these solvents raise issues because of their high price and toxicity to aquatic life and humans, as well as their negative effects on the environment. It is essential to replace these risky organic solvents with safer and more affordable alternatives in accordance with the principles of white analytical chemistry to protect aquatic life, and the environment.MethodsIn order to assess numerous fixed-dose combinations of paracetamol simultaneously, a white analytical chemistry-driven RP-HPLC method has been developed. This approach maintains a single chromatographic condition while using economical and ecologically acceptable solvents. The development of the RP-HPLC method attempts to reduce waste generation during chromatographic analysis by implementing the principles of analytical quality by design.ResultsThe Taguchi OA and Box-Behnken design were used to optimize the targeted RP-HPLC method. The validation efficiency, greenness profile, time efficiency, and cost efficiency of the published and suggested RP-HPLC methods were assessed using principles of white analytical chemistry.ConclusionThe proposed RP-HPLC approach was found to be cost-efficient, quick, robust, and environmentally friendly for the simultaneous determination of multiple fixed-dose combinations of paracetamol.