Chemometrically assisted optimization, development and validation of UPLC method for the analysis of simvastatin

Abstract

This manuscript presents chemometrically assisted optimization and validation of UPLC method intended for the quantitative analysis of simvastatin in pharmaceutical preparations. To achieve the desired chromatographic response and to simultaneously optimize the most important chromatographic parameters with a limited number of experiments in a minimum amount of time, Box-Behnken design was used. The separation was performed on Poroshell 120 EC C18 50 x 3.0 mm 2.7 μm, using 10 mM ammonium formate pH 4.0 and acetonitrile as the mobile phase. To obtain complete information about method performance and robustness, seven factors (column type, acetonitrile content, temperature, pH of mobile phase, molarities of ammonium formate, flow rate and wavelength) were assessed in twelve experiments according to Plackett–Burman design. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines to confirm specificity, linearity, precision, detection and quantification limits. Validation results have shown that the proposed method is selective, linear, accurate, sensitive (LOD 0.06 μg/mL and LOQ 0.18 μg/mL), and robust and it is suitable for quantitative determination of simvastatin in pharmaceutical preparations. The optimized and validated method gives rapid and efficient separation and represents an improvement over the existing methods especially in the terms of sensitivity, low cost of analysis per sample and the environmental impact of the method. Keywords: chemometry, design of experiments, UPLC/DAD, simvastatin