Enantiomeric Separation of S-Epichlorohydrin and R-Epichlorohydrin by Capillary Gas Chromatography with FID Detector

The aim of this study was to develop a simple and derivatization free method for the Quantification of S-Epichlorohydrin in R-Epichlorohydrin by using a gas chromatography coupled with flame ionization detector (FID). Enantiopure epichlorohydrin was a valuable epoxide key starting material for preparing optically active Rivaroxaban. The enantiomeric separations of S-Epichlorohydrin and R-Epichlorohydrin were achieved on Gamaa-Dex-225 (30 meters × 0.25 mm I.D, 0.25 μm) column with a total run time of 30 min. Nitrogen was used as a carrier gas with constant pressure 25.0 psi. The critical experimental parameters such as, column selection, flow rate, injection volume and diluent were studied and optimized. Excellent correlation coeffient between peak responses and concentrations was >0.9998. The recoveries of S-Epichlorohydrin spiked in R-Epichlorohydrin were in the range from 98.2% to 102.8%. Limit of quantitation for S-Epichlorohydrin was sufficiently lower than limits specified by ICH. The method has validated as per International Conference on Harmonization (ICH) guidelines. A precise, accurate, linear and robust Gas Chromatography method was developed for the quantification of S-Epichlorohydrin in R-Epichlorohydrin for Rivaroxaban.

A New and Enantioselective Chromatographic Method for Linagliptin on Amylose Coated Chiral Stationary Phase

A new and enantioselective liquid chromatographic method was developed for estimation of S-Linagliptin in Linagliptin (LINA) drug substances. The desired enantiomeric separation was achieved on Chiralpak AD-H (250*4.6 mm*5 μm) column with the mobile phase composition of ethanol, methanol and diethylamine in a ratio of 90:10:0.1 (v/v/v) with flow rate of 0.5 mL·min-1 and column oven temperature 30°C and the eluted compounds were monitored at 225 nm. In the proposed chiral method, USP resolutions between both the enantiomers were more than 5.0. Limit of detection and Limit of quantitation of S-LINA was found to be 0.03 μg·mL-1 and 0.10 μg·mL-1 respectively. Linearity study was conducted from LOQ to 150% and correlation coefficient found to be 0.9997. Accuracy was within the range of 98.6% to 101.5%. To prove selectivity power of the method specificity study was conducted by subjecting drug substance to acid, base, hydrolysis, oxidation and photolysis and ensured the peak purity of analyte in degraded samples. Moreover, the method has been fully validated as per ICH guidelines. The proposed method is precise, accurate, linear, rugged, robust and suitable for accurate quantification of S-LINA in LINA drug substance.

Validated Gradient Stability Indicating UPLC Method for the Determination of Related Substances of Posaconazole in Bulk Drug

A stability-indicating UPLC method has been developed and validated for the determination of related substances of Posaconazole with its four related substances (Hydroxytriazole, Tosylated compound, Deshydroxy posaconazole and Benzylated posaconazole) in the drug substance. Forthwith simple UPLC chromatographic separations were achieved on a Waters Acquity BEH shield C18 (100 mm length, 2.1 mm internal diameter and 1.7 μm particle size) with a mobile phase containing 0.1% Orthophosphoric acid (i.e. 1 mL in 1000 mL water) in gradient combination with acetonitrile (ACN) at a flow rate of 0.5 mL/min and the eluent were monitored at 210 nm. As a result, the resolution of Posaconazole from any of impurities was found to be greater than 2.0. The test solution and spiked solutions were found to be stable in the diluent for 48 h. For the purpose method to be stability indicating, forced degradation studies were conducted and the method resolved the drug from its known impurities, stated above, and from additional impurities generated when POS subjected to forced degradation;the mass balance was found close to 100%. Regression analyses indicate correlation coefficient value greater than 0.999 for Posaconazole and its known impurities. The LOD for Posaconazole and the known impurities was at a level below 0.05%. The method has shown good, consistent recoveries for known impurities (89% - 106%). To summarise, the method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and stability-indicating.