Riluzole: Validation of Stability-Indicating HPLC, D1 and DD1 Spectrophotometric Assays

Abstract

A stability-indicating reversed-phase high-performance liquid chromatographic assay procedure has been developed and validated for riluzole in the presence of alkaline and oxidative degradation products. The liquid chromatographic separation was achieved and compared isocratically on C18 Zorbax ODS and Poroshell 120 EC-C18 columns by using a mobile phase containing methanol-water, pH = 3.10 (70:30, v/v), at a flow rate of 1 mL/min and ultraviolet detection at 264 nm. The method was linear over the concentration ranges of 20-200 µg/mL (r = 0.9997) and 10-200 µg/mL (r = 0.9995). The limit of detection and quantitation for the two columns were 2 and 6 µg/mL and 1 and 3 µg/mL, respectively. Moreover, spectrophotometric methods were applied for the determination of riluzole in the presence of its oxidative degradation products by using first derivative spectrophotometry at 252.5 and 275.0 nm. The method was linear over the concentration range of 1-20 µg/mL (r = 0.9995 and 0.9996) at the studied wavelengths, with limits of detection and quantitation of 0.1 and 0.3 µg/mL. In addition, the first derivative ratio spectrophotometry (DD1) method was applied for the determination of riluzole in the presence of its alkaline degradation product at 252.0, 278.5 and 306.3 nm by using 100 µg/mL of alkaline degraded riluzole as a divisor; riluzole was additionally determined in the presence of its hydrogen peroxide oxidative degradation products at 252.5, 275.0 and 305.0 nm by using 200 µg/mL of oxidative degraded riluzole as a divisor. The DD1 method was linear over the concentration range of 1-20 µg/mL (r = 0.9996, 0.9995 and 0.9996 for the alkaline degradation product at the three studied wavelengths, respectively; and r = 0.9995, 0.9996 and 0.9995 for the oxidative degradation product at the three studied wavelengths, respectively), with limits of detection and quantitation of 0.1 and 0.3 µg/mL for both alkaline and oxidative degradation products. The two studied chromatographic and spectrophotometric methods were comparable and display the required accuracy, selectivity, sensitivity and precision to assay riluzole in bulk and pharmaceutical dosage forms. Degradation products resulting from the stress studies did not interfere with the detection of riluzole, which indicates that these are stability-indicating assays.