Response surface methodology combined Box-Behnken design optimized green kinetic spectrophotometric and HPLC methods...

The high-performance liquid chromatographic (HPLC) and kinetic spectrophotometric methods were established to compute valsartan (VAL) in pharmaceutical formulations. The spectrophotometric procedures adopted initial rate, fixed time, and equilibrium strategies to assess VAL. The method was based on the carboxylic acid group of the oxidized VAL with a mixture of potassium iodate (KIO₃) and potassium iodide (KI) at room temperature, producing a stable, yellow-coloured absorb at 352 nm. The critical parameters were optimized using green process optimization methodology such as Box-Behnken design (BBD) which belongs to response surface methodology (RSM). After the screening, experiments identified them as significant, and then three crucial factors were optimised: KI volume, KIO₃ volume, and reaction time against response as absorbance. The HPLC procedure was also optimized based on the desirability function on RSM-BBD. The parameters such as pH, methanol (%), and flow rate (ml/min) were optimized with the best responses: peak area, symmetry, and theoretical plates. The linearity of spectrophotometric and HPLC methods was within the range of 2-24 and 0.25-11.25 µg/ml, respectively. The developed procedures produced excellent accuracy and precision. The design of the experiment (DoE) setting explained and discussed the individual steps and the importance of independent and dependent variables used to develop the model and optimization. The method was validated as per the International Conference on Harmonization (ICH) guidelines. Furthermore, Youden's robustness study was applied with factorial combinations of the preferred analytical parameters and explored their influence with alternative conditions. The analytical Eco-Scale score was calculated and was found a better option as green methods to quantify VAL. The results were reproducible with the analysis completed with biological fluid and wastewater samples.