Chemometrics‐Assisted Spectrophotometric Methods for Determination of Methocarbamol and Paracetamol Along With Two Related Impurities: An Environmental Sustainability Assessment

ABSTRACT Two multivariate calibration models were created for the concurrent estimation of methocarbamol and paracetamol in their co‐formulated pharmaceutical dosage form. These methods also enabled the detection of their impurities, p ‐aminophenol and guaifenesin. The calibration paradigms, based on principal component regression (PCR) and partial least squares (PLS), were employed to assess the drugs and their impurities. The methods demonstrated accurate simultaneous determination of methocarbamol, paracetamol, p ‐aminophenol, and guaifenesin within the concentration ranges of 20.00–80.00 µg mL −1 for methocarbamol, 20.00–60.00 µg mL −1 for paracetamol, 0.06–4.00 µg mL −1 for p‐ aminophenol, and 0.08–10.00 µg mL −1 for guaifenesin. The techniques were evaluated in accordance with ICH directions, and the outcomes confirmed the reliability and validity of the developed methods. The suggested approaches were successfully applied to analyze methocarbamol and paracetamol in their combined tablets and to quantify their related impurities. Furthermore, the environmental impact of these techniques was evaluated using a variety of metrics, assessing their greenness and whiteness alongside their practical effectiveness (blueness), with the results highlighting their superior environmental performance. Additionally, the suggested techniques' sustainability was appraised using the recently introduced NQS index, yielding a score of 67.70%, demonstrating strong alignment with sustainable analytical practices.