Development of a Stability-Indicating RP-UPLC Method for Rapid Determination of Metaxalone and its Degradation Products in Solid Oral Dosage Form

摘要

A simple, sensitive and reproducible reversed phase ultra performance liquid chromatography (RP-UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of metaxalone (META) in pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assay of drug product. Chromatographic separation was achieved on an Acquity^® HSS-T3 (100 mm x 2.1 mm, 1.7 μm) column. The optimized isocratic mobile phase consists of a mixture of water, methanol, acetonitrile and triethylamine in the ratio of 50:25:25:0.1 % v/v (pH adjusted to 6.3 with orthophosphoric acid). The eluted compounds were monitored at 230 nm for META assay and 205 nm for related substances, the flow rate was 0.3 mL/min, and the column oven temperature was maintained at 45°C. The developed method separated META from its two known and two unknown impurities within 6.0 min. Metaxalone was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Metaxalone was found to degrade significantly in base stress condition, degrade slightly in oxidative stress condition and remain stable in acid, hydrolytic, thermal and photolytic degradation conditions. All impurities were well resolved from each other and from the main peak, showing the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines.