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

Background: Erdosteine is a mucolytic drug and has antioxidant activity.

Objective: The study aimed to develop an HPLC method for determination of erdosteine and its impurities in erdosteine bulk drug and to 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 (250 mm × 4.6 mm id, 5 μm). Acetonitrile-0.01 mol/L citric acid solution (13 + 87, by volume) pumped at a flow rate of 1.0 mL/min was used as the mobile phase. The detection wavelength was 254 nm. Two main impurities in erdosteine bulk drug were enriched by an ODS column chromatography and oxidative degradation, respectively, and then both were purified by semipreparative HPLC. Finally, their structures were identified by a variety of spectral data (MS, 1H NMR and 13C NMR).

Results: Good separations of 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 was produced in the refining process of erdosteine bulk drug when using ethanol as a 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: An HPLC method for determination of erdosteine and its related impurities was developed and validated. Two main impurities in erdosteine bulk drug were isolated and identified. Avoiding ethanol as the 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.