Second-derivative UV spectrometric determination of simvastatin in its tablet dosage form

Simvastatin, a highly effective cholesterol-lowering agent, has been widely used for the treatment of hypercholesterolemia. During the development of simvastatin solid dosage form, formulation compositions were constantly varied to define a suitable matrix. A fast and reliable method for the dissolution and release testing of simvastatin was highly desirable to support formulation screening. A second derivative UV spectroscopic method was developed for determination of simvastatin in the tablet dosage form. After carefully choosing a zero-crossing technique of second derivative UV measurement at 243 nm, the selectivity and sensitivity of simvastatin was comparable to the previously developed HPLC method. In comparison with the direct UV method, second derivative UV spectroscopy eliminates the interference from UV absorbing excipients such as ascorbic acid, which often results in a bias of 2-10%. This method is also fast and economical in comparison to the more time-consuming HPLC method regularly used for formulation screening. Finally, this method has been validated to be precise and accurate, and is demonstrated to be an excellent alternative to HPLC method for the dissolution and release testing of simvastatin in the solid dosage form. (C) 2000 Elsevier Science B.V. All rights reserved.