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.

中文翻译：

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厄多司坦原料药中相关杂质的测定、分离和鉴定

背景 厄多司坦是一种粘液溶解药物，具有抗氧化活性。目的建立测定厄多司坦原料药中厄多司坦及其杂质的高效液相色谱法，鉴定主要杂质，以帮助提高厄多司坦原料药的质量。方法 色谱分离在 CAPCELL PAK C18 色谱柱（4.6 mm × 250 mm id，5 μm）上进行。以 1.0 mL/min 的流速泵送的乙腈–0.01 mol/L 柠檬酸溶液 (13:87, v/v) 用作流动相。检测波长为 254 nm。分别采用ODS柱色谱法和氧化降解法富集厄多司坦原料药中的两种主要杂质，然后均采用半制备型HPLC纯化。最后，通过各种光谱数据（MS、1H NMR 和 13C NMR）鉴定了它们的结构。结果 观察到厄多司坦及其相关杂质的良好分离。经证实，一种新杂质为醋酸乙酯（{2-氧代-2-[（2-氧代四氢-3-苯硫基）氨基]乙基}硫烷基）酯，即厄多司坦乙酯，在厄多司坦原料药精制过程中产生。使用乙醇作为精制溶剂。另一种杂质被证实为({2-氧代-2-[(2-氧代四氢-3-噻吩)氨基]乙基}亚磺酰基)乙酸，它是一种厄多司坦氧化物。结论建立并验证了测定厄多司坦及其相关杂质的高效液相色谱法。分离鉴定了厄多司坦原料药中的两种主要杂质。避免乙醇作为精制溶剂可以提高厄多司坦原料药的纯度。