Assessment of the hydrolytic degradation of lovastatin by HPLC

Abstract

In this work an HPLC stability-indicating method was developed and applied to study the hydrolytic behaviour of lovastatin in different simulated fluids. The selected chromatographic conditions were a C-18 column, acetonitrile/methanol/phosphate buffer solution pH 4 (32/33/35) as mobile phase, 45 degrees C temperature column, flux of 1.5 mL/min and UV detection at 238 nm. The developed method exhibited an adequate repeatability and reproducibility (CV 0.057% and 0.73%, respectively) and a recovery higher than 98%. Furthermore, the detection and quantitation limits were 9.1 x 10(-7) M and 2.8 x 10(-6) M. Lovastastin exhibited a pH-dependent degradation with an instantaneous hydrolysis in alkaline media at room temperature. One or two degradation products could be observed when lovastatin is hydrolyzed in alkaline or acid medium, respectively. The degradation products from lovastatin retain the UV-spectra of the parent drug, evidencing that the chromophore structure remains unaltered. Also, lovastatin hydrolysis in different media follows a pseudo first-order kinetic. The rank-order for lovastatin stability in different media was: simulated gastric medium without pepsin > 0.06 M HCl > 0.1 M HCl > phosphate buffer pH 7.4 + sodium laurylsulphate > phosphate buffer pH 7.4.