Stability-indicating HPLC method development and validation of rivaroxaban impurities and identification of forced degradation products using LC-MS/MS.

The current aim of this study is to develop a simple, sensitive, and robust analytical method that can separate the Rivaroxaban and its related impurities by using HPLC. This new method can separate enantiomers and all the process-related impurities of rivaroxaban. This method can also be used to determine the assay of rivaroxaban in drug substances and drug products. This new method was developed using a Chiralpak IC (250 × 4.6 mm, 5 µm) column at 27°C with a gradient program of 25.0 min at a flow rate of 0.8 mL/min. Mobile phase A consisted of acetonitrile, ethanol, and n-butyl amine in the ratio of 95:5:0.5 (v/v/v), respectively. Mobile phase B consisted of a mixture of Milli-Q water, methanol, and n-butyl amine in the ratio of 50:50:0.5 (v/v/v), respectively. The detector wavelength was 254 nm. Rivaroxaban was subjected to the forced degradation conditions (stress conditions) of hydrolysis, base, acid, thermal, photolysis, and oxidation. The degradation products were well separated from rivaroxaban peak and enantiomer peak, and its potential impurities prove the stability-indicating power of the method. The proposed new stability-indicating method was validated with respect to specificity, precision, accuracy, limit of quantification, limit of detection, linearity robustness, and roundness per International Conference on Harmonization guidelines. The %RSD (relative standard deviation) for six sample preparations for rivaroxaban and impurities less than 10% and the recovery is between 90 and 110%. The current method can be used in quality control labs for analysis of commercial products.

Novel dermacozine-1-carboxamides as promising anticancer agents with tubulin polymerization inhibitory activity.

In the present study, novel dermacozine-1-carboxamides (8a-8n) were synthesized and screened for their in vitro cytotoxic activity against three different cancer cell lines: MCF-7 (breast cancer), A-549 (lung cancer) and DU145 (prostate cancer). All the compounds showed more efficiency against the DU145 cell line than against the MCF-7 and A-549 cell lines. Furthermore, 8a (CTC50: 7.02 µM) and 8l (CTC50: 6.32 µM) have been found to be more effective against the DU145 cells as they arrest the cell cycle at the G2/M phase by interfering with tubulin polymerization; these results indicate that these compounds act as potential anti-cancer agents by inhibiting tubulin polymerization.