Determination, Isolation, and Identification, of Related Impurities in Erdosteine Bulk Drug

Abstract

Abstract Background Erdosteine is a mucolytic drug and has antioxidant activity. Objective To develop a HPLC method for determination of erdosteine and its impurities in erdosteine bulk drug and identify the main impurities to help improve the quality of erdosteine bulk drug. Method The chromatographic separations were performed on a CAPCELL PAK C18 column (4.6 mm × 250 mm i.d., 5 μm). Acetonitrile–0.01 mol/L citric acid solution (13:87, v/v) pumped at a flow rate of 1.0 mL/min was used as the mobile phase. Detection wavelength was 254 nm. Two main impurities in erdosteine bulk drug were enriched by ODS column chromatography and oxidative degradation, respectively, and then both were purified by semi-preparative HPLC. At last, their structures were identified by a variety of spectral data (MS, 1H NMR and 13C NMR). Results Good separations for erdosteine and its related impurities were observed. A new impurity was confirmed as ethyl ({2-oxo-2-[(2-oxotetrahydro-3-thiophenyl) amino] ethyl} sulfanyl) acetate, which was erdosteine ethyl ester, and produced in the refining process of erdosteine bulk drug when using ethanol as refining solvent. Another impurity was confirmed as ({2-Oxo-2-[(2-oxotetrahydro-3-thiophenyl) amino] ethyl} sulfinyl) acetic acid, which was an erdosteine oxide. Conclusions A HPLC method for determination of erdosteine and its related impurities is developed and validated. Two main impurities in erdosteine bulk drug were isolated and identified. Avoiding ethanol as refining solvent can improve the purity of erdosteine bulk drug. Highlights A new process related impurity and an oxidative degradation impurity in erdosteine bulk drug were isolated and identified.