Development and validation of a stability-indicating RP-HPLC method for the determination of fifteen impurities in rivaroxaban.

ABSTRACT

A simple and stability-indicating reverse phase high-performance liquid chromatographic (RP-HPLC) method for the determination of rivaroxaban (RIX) and its related substances was developed. Fifteen impurities of RIX, including three unreported isomers, were identified, synthesized, purified, and confirmed using MS, 1H NMR, 13C NMR, and HSQC spectral methods. This new method offered baseline separation for all monitored impurities, and was fast and reliable when compared to the European Pharmacopoeia method. Optimum separation for RIX and its related impurities was achieved on an octyldecyl silica column (YMC Core C18, 4.6 ×100 mm, 2.7 µm) by using a gradient HPLC method in 38 min. The final method was validated with respect to precision, LOD and LOQ, linearity, accuracy, and robustness. This developed method was suitable for routine quality control and drug analysis of RIX active substance.