Stability-Indicating Determination of Rebamipide in the Presence of its Acid Degradation Products

Abstract

Abstract Four sensitive and precise stability-indicating methods for the determination of rebamipide (REB) in the presence of its acid-degradation products and ina pharmaceutical formulation were developed and validated. Method A used the first derivative of the ratio spectra (1DD) spectrophotometric method by measuring the peak amplitude at 249.4 nm (maximum) and at 259 nm (minimum), and at the total peak amplitude (from 249.4 to 259 nm, 1DD249.4 + 259 nm) in the range of 2–14 μg/mL. This method yielded mean recoveries of 99.87 ± 0.83, 100.04 ± 0.75, and 100.28 ± 1.11%, respectively. Method B is a dual wavelength method, which allows the determination of REB in presence of its acid-degradation products by measuring the absorbance difference between 254 and 269 nm within a linearity range of 5–65 μg/mL; it showed a mean recovery of 99.84 ± 1.06. Method C is a TLC-densitometric procedure in which REB was separated from its degradation products using a developing solution of methanol–chloroform–ammonia (8.5 + 1.5 + 0.5, v/v/v). The quantitative evaluation of REB at 329 nm was linear over the concentration range of 0.50–4.5 μg/band, with a mean recovery of 99.49 ± 0.99% even in the presence of up to 90% degradation products. Method D is an RP-HPLC procedure. It provided the complete separation of REB from its degradation products on an XterraTM C18 column using phosphate buffer (pH 6, 0.01 M)–methanol (1 + 1, v/v) as the mobile phase (UV detection at 254 nm). Recovery was 99.28 ± 0.78% within the range of 10–190 μg/mL. The selectivity of the proposed methods was checked using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of REBin pharmaceutical dosage forms without interference from other dosage form excipients.