Gradient Mode HPLC Approach to Quantify Sodium Bisulfite as an Antioxidant in Raw Material and in Oral Pharmaceutical Suspension Containing Parabens and Nystatin; Utilization of Greenness Tools

Antioxidants can maintain the medication's quality throughout production and storage, with acceptable limits during shelf life potentially being lower than release limits, provided that other quality attributes are met; they may reach to be NLT 5 % (or lower) from the target amount in the medication formula at shelf life which may reach to be totally consumed within a short period of time like within a month from the manufacturing process time. Sodium bisulfite (SBS) is used as a chemical preservative and antioxidant in oral suspensions containing nystatin, methylparaben sodium, and propylparaben sodium. SBS itself isn't the active therapeutic ingredient, its role as a preservative/antioxidant is therapeutically critical for maintaining the efficacy and safety of the drug product. By developing and validating a complete, innovative, fast, gradient, and green shelf life liquid chromatography methodology, sodium bisulfite levels in oral suspensions can now be measured. The challenges that were faced during the method development are; the matrix interference effect with the SBS main peak while considering isocratic method and the long run time, so we relied on the current gradient mode, moreover the reliance on usage of the current specific column with the low particle size was the best choice to get the well resolved SBS peak, additionally the preclusion of ethanol which is greener than acetonitrile was owing to the high back pressure of ethanol on the column's small particle size and the interference that was resulted with the sample matrix with ethanol. A number of tests were performed on the antioxidant compound in accordance with ICH and US FDA guidelines. Sodium bisulfite and its related degradants were effectively separated via gradient separation. At room conditions, the Shim-pack C-18 stationary phase was used to quantify and validate the antioxidant. The gradient mobile phase runs at a flow rate of 1.0 mL/min. It includes varying concentrations of phosphate buffer at pH 2.5 and acetonitrile. The positive environmental impacts of the LC technique are demonstrated by the combined Eco Scale (AES) grade of 90, Analytical Greenness Metric technique (AGREE) grade of 0.63, Analytical Greenness Metric for Sample Preparation (AGREEprep) rating of 0.62, Click Analytical Chemistry Index (CACI) rating of 64, Analytical Green Star Area (AGSA) rating of 63.89, Modified Green Analytical Procedure Index (MoGAPI) rating of 82, Blue Applicability Grade Index (BAGI) rating of 77.5, and final whiteness rating of 95.8. Concerning the current paper, the proposed methodology is unique and true, with a recovery percentage range of 97.67 to 99.1 %; linear within the range of 10–200 μg/mL with a correlation coefficient R 2 of 0.99978; strong, with an average inter-day precision of 100.62 % and a pooled RSD% < 2 %, and an average intra-day precision of 100.67 % with a pooled RSD% < 2 %; sensitive, with a detection limit of 3.22 μg/mL and a quantitation limit of 9.77 μg/mL; and environmentally beneficial, making it suitable for regular quality control inspections.