Modeling/Optimization of a RP-HPLC Method via Response Surface Strategy: A Case Study on the Analysis of Paracetamol in Tablet dosage forms
Within the present work, response surface methodology (RSM), based on a Box-Behnken design was successfully applied to develop a reverse phase high-performance liquid chromatography (RP-HPLC) method in which paracetamol was analyzed and determined on a C18 column (250 × 4.6 mm, 5 μm) with UV detection at 243 nm. To explain more, RSM was used to statistically model the impact of three independent factors as flow rate (mL.min-1) (A), column temperature (°C) (B) and mobile phase composition (H2O:MeOH) (C) on the retention time (Rt) of Paracetamol. Analysis of variance (ANOVA) introduced solvent ratio as the most significant model term and it was also revealed that all of the factor levels were indirectly proportional to the Rt. Moreover, the interference of column temperature (B) and solvent ratio (C) seemed to be the most significant interactive model term. It could be concluded that flow rate (A) and mobile phase composition (B) did not have a detectable interaction with each other and hence the relevant factor effects on response could be studied independently without regarding any serious interferences. It was also predicted that optimum assay condition included 1:2 ratio of methanol to water, column temperature of 35ºC and mobile phase flow rate of 1.3 mL.min−1. Using this optimum condition, baseline separation of the drug was achieved with a good resolution and a run time of 2.1 min. The optimized method was validated in terms of linearity, accuracy, limit of detection and limit of quantification. The method was subsequently applied within a few commercially available paracetamol tablets. Finally, in an attempt to determine the best combination of factors toward better responses, desirability function (with all factor levels in the range) was used to introduce a set of optimized solutions leading to paracetamol retention times of 2.083 to 2.099 min.
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