The Related Substances Methodology Study Of Rivaroxaban

Rivaroxaban is an oral antithrombotic drug developed by Bayer, which is5-chloro-N-({(5S)-2-oxo-3-[4-Phenyl)-1, 3-oxazolidin-5-yl} methyl)-2-thiophene-carboxamide as an oral medicament with a high selectivity inhibitory factor Xa for the treatment of selective hip or knee Joint replacement surgery for the prevention of venous thromboembolism(VTE).Rivaroxaban is a relatively safe drug, but it has anti-hemostatic effect as well as anti-thrombotic effect. In some special clinical situation, monitored to ensure that it at the same time. So it is still necessary to be monitored to ensure that it does not increase the risk of bleeding while anti-thrombosis in some special clinical conditions.Therefore,.it is very important to control the related substances of the raw materials of Rivaroxaban and detect the impurities.In this paper, the existing process of the synthesis was compared. We did some analysis and detection of related substances for the synthesis of raw materials of Rivaroxaban in the current industrial production process. The research was studied on the condition of the raw materials, by-products, intermediates and degraded impurities of the synthetic route.In the synthetic route of Rivaroxaban, there were 14 possible substances to be identified by liquid chromatography, Through different analytical methods,and a series of detailed methodological studies we confirmed the feasibility of this chromatographic condition.Reversed phase high performance liquid chromatography(RP-HPLC) and diode array detector were used to detect the related substances of Rivaroxaban, namely,Thermo Hypersil BDS C-18 column(150mm×4.6mm, 5?m). The column temperature was 40?, and the detection wavelength was 250 nm, and the mixture solution(1.36 g potassium dihydrogen phosphat and 1.0g hexane sulfonate sodium salt and 0.2ml 85%phosphoric acid water diluted to 1000ml) : methanol(95: 5) was mobile phase A,acetonitrile :water(90:10) was the mobile phase B, gradient elution;The relevant substance detection method can effectively detect the relevant impurity in Rivaroxaban, The results are accurate and reliable so it could control the quality of the product. and ensure the safety of Rivaroxaban. Therefor it has important guiding significance for the industrial production of Rivaroxaban.