24 INDIAN DRUGS 51(11) NOVEMBER 2014 A vALIDATED METHOD DEvELOPMENT FOR ESTIMATION OF SIMvASTATIN By FIRST ORDER DERIvATIvE SPECTROSCOPy Dubey S*., Shukla S. S. (Received 19 June 2014) (Accepted 11 November 2014) ABSTRACT Simvastatin is a hypolipidemic drug used with exercise, diet, and weight-loss to control elevated cholesterol, or hypercholesterolemia. It is a member of the statin class of pharmaceuticals. Simvastatin is a synthetic derivative of a fermentation product of Aspergillus terreus. The drug is marketed generically following the patent expiration, and under the trade name Zocor. The aim of this study is to develop a simple, accurate, precise and economical procedure for estimation of Simvastatin by first order derivative spectroscopy. The method is based upon determination of D1 value of the drug at, in Methanol. Different analytical performance parameters such as linearity, range, system precision, robustness, sensitivity and accuracy were determined according to the ICH guidelines. Simvastatin at its λ max shows linearity in the concentration range 10-60μg/mL. Keywords: Simvastatin, UV spectroscopy, 1st order derivative spectroscopy, method development and validation. INTRODUCTION Simvastatin {SIM} (1S,3R,7S,8S,8aR)-8- {2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7- dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2- dimethylbutanoate is a lipid-lowering agent that is derived synthetically from the fermentation of Aspergillus terreus 1 . It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol. It belongs to a class of drugs called HMG- CoA reductase inhibitors, commonly called “statins.” Other statins include lovastatin (Mevacor), atorvastatin (Lipitor), fluvastatin (Lescol),and rosuvastatin (Cresto)Statins reduce cholesterol by inhibiting an enzyme in the liver (HMG-CoA reductase) that is necessary for the production of cholesterol. In the blood, statins lower total and low density lipoprotein (LDL) or “bad” cholesterol as well as triglycerides. LDL cholesterol is believed to be an important cause of coronary artery disease 2 . Lowering LDL cholesterol levels slows and may even reverse coronary artery disease. Statins also increase high density lipoprotein (HDL) or “good” cholesterol. Raising HDL cholesterol levels, like lowering LDL cholesterol may slow coronary artery disease. The FDA approved Simvastatin in December, 1991 3 . Fig. 1: Structure of Simvastatin Determination of Simvastatin by various analytical methods like 2 nd order derivative spectrophotometric method, UPLC 4 , gas chromatography mass spectroscopy (GC-MS) liquid chromatography with UV detection and simultaneous methods with drugs like sitagliptin have been reported 5,6 . But these methods are sophisticated, expensive and time consuming when compared to simple UV spectrophotometric method 7 . There is a need for a simple, rapid, cost effective and reproducible method for assay of Simvastatin in its dosage forms. Therefore, it was thought of interest to develop a simple, speedy, accurate and cost effective method for the analysis of Simvastatin in its tablet formulation. This paper describes development *For correspondence: Lafarge Cement plant, Sonadih - 221 715, Dist. Baloda Bazar, C.G. Email: dubeyswati326@gmail.com