Development of methodologies based on HPLC and Raman spectroscopy for monitoring the stability of lovastatin in solid state in the presence of gallic acid.

Abstract

Methodologies based on FT-Raman spectroscopy and HPLC were developed for monitoring the stability of lovastatin in the solid state in the presence of gallic acid, a natural antioxidant. A Raman calibration curve was constructed using the area of the strong but overlapping vibration mode of lovastatin at 1645 cm(-1) and of the gallic acid at 1595 cm(-1). Mixtures of the active ingredient with the antioxidant were heated in the presence of atmospheric air up to 120 degrees C. The molar ratios of lovastatin and gallic acid in the artificially oxidized mixtures were determined from their Raman spectra using the calibration curve. The results were compared to those obtained from the application of the HPLC methodology and found to match satisfactorily. The HPLC analysis was based on a reserved-phase Zorbax C(g), 10 microm (4.6mm x 25 cm i.d.) column, using a gradient elution program by varying the proportion of solvent A acetonitrile 100% to solvent B 0.1% v/v phosphoric acid, and a programmable diode array detection at 225 nm. The Raman methodology was simpler and non-destructive for the sample but yielded only molar ratios as opposed to the HPLC technique where the moles of the both ingredients were determined.