Rational Design of Colorimetric Reagent for Sensitivity and Selectivity Enhancement for β Hydroxy Acid of Simvastatin

Simvastatin is used in the treatment of hypercholesterolemia as β hydroxy acid of simvastatin (BHA) which inhibits 3-hydroxy methyl glutaryl coenzyme A involved in cholesterol synthesis. The present communication deals with the development of colorimetric method for estimation of BHA through rational design of colorimetric reagent for sensitivity and selectivity enhancement. BHA is an active metabolite as well as impurity of simvastatin, synthesized by alkaline hydrolysis of simvastatin. In the developed colorimetric method, improvement in the sensitivity of quantification of BHA was found to be more than 660 folds. The detector response for BHA in colorimetric method was found to be linear in concentration range of 0.1- 3.2ng/mL. This method was validated using ICH Q2B (R1) guidelines. The reported method is found to be simple, precise, accurate, rapid and economic for quantification of BHA. The colorimetric method can be optimized further for quantification of BHA in simvastatin formulations and in plasma. Keywords: β hydroxy acid, colorimetry, 4-nitro phthalic anhydride, simvastatin, sensitivity, selectivity.