An Experimental Design Approach for Method Development and Impurity Profiling of Simvastatin by UV Spectrophotometric and RP–HPLC Methods

Abstract

Analytical method development is a vital part of pre-formulation and formulation development research.
Development of validated, robust, cost-effective methodologies for routine drug estimations is the urgent need
of the pharmaceutical R&Ds. Quality is an essential attribute in any pharmaceutical product and impurity
profiling offers a broad scope with the changed perspectives of the research scenario. The present work aims to
devise a validated UV-spectroscopic and RP–HPLC method for estimations of SVN in bulk and formulations
and impurity profiling of SVN related impurities at the specification limit with the aid of response surface
methodology. The percent assay for SVN determined by UV method was 100.4±0.15 and mean %recovery was
achieved to be 99.87±0.19. The percent assay of SVN by RP-HPLC method was found to be 100.14±0.1. The
mean percent recovery at different spike levels (50–150%) ranged from 97.3±0.01–100.5±0.02 and the %RSD
of assays at lower and higher spike levels were 1.4 and 0.3 respectively. The linearity data of impurities (A–G)
at different spike levels (25, 50, 100, 125 and 200 µg) showed a high correlation coefficient of 0.99 in all cases.
Percent mean recovery of impurities (A–G) at different spike levels comply the acceptance criterion. All other
validation parameters also comply within the range of acceptable limits. The impurities were well separated
with good resolution and peak shape, good retention times. The robustness of the developed HPLC method and
that of impurity profiling was optimized applying Box-Benkhen experimental design approach.