The Application of Box-Behnken-Design in the Optimization of Kinetic Spectrophotometry and Computational Studies to Determine and Assessing Eco-Scale to Green Analytical Chemistry for Labetalol

The study is aimed at the quantitative analysis of Labetalol utilizing Box-Benken design, where higher order response surfaces are generated and optimized for a significant model using fewer runs than a usual factorial technique. The kinetic spectrophotometric methods were established to compute labetalol in pharmaceutical formulations. Initial rate and fixed-time methods were developed to determine labetalol with the mixture of potassium iodate and potassium iodide at room temperature to produce a stable yellow-coloured product that absorbs at 351 nm. The optimization was reached using the Box-Behnken experimental design involving response surface methodology. Four significant factors were investigated: labetalol volume, reaction time, potassium iodate and potassium iodide volume against response absorbance. The two and three-dimensional response surface plots revealed the significance of each parameter on the response and the correlation between them. The importance of statistical analysis and polynomial equations on the model’s efficacy. The developed method was also validated according to International Conference on Harmonization guidelines, and outcomes were accurate and precise within the limit. The linearity was in the range of 0.25–49.9 µg/mL. The analysis of the different calibrations suggests excellent linearity ranging from 0.9928-0.9988. The limit of detection (LOD) and limit of quantitation (LOQ) are in the range of 0.28-0.35 µg/mL and 0.92-1.16 µg/m, respectively. In comparing the proposed method with the reference one, the recovery ranges of the initial rate, fixed time and the reference methods were in the range of 99.34–99.57, 99.43-99.56, and 98.56-98.99, respectively. The proposed method is simple, environmentally friendly, and involves cost-effective instruments. The proposed method’s greenness report was compared to the reference-reported traditional methods using the analytical Eco-Scale evaluation tool. The reported approach was greener regarding using perilous reagents, energy consumption, and waste production. Therefore, the proposed strategies could be safely applicable in pharmaceutical formulations, biological fluids, and wastewater samples to quantify labetalol.