Liu Heying, Xiong Xin, Wang Jie, Pei Kun, Zhong Zhenhua, Zhou Zhiqiang, Cheng Qizhen
Chemical Laboratory of Jiangxi Institute for Drug Control, NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine, Jiangxi Province Engineering Research Center of Drug and Medical Device Quality, Nanchang 330029, China.
J AOAC Int. 2022 Apr 27;105(3):696-702. doi: 10.1093/jaoacint/qsab131.
Erdosteine is a mucolytic drug and has antioxidant activity.
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.
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).
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.
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.
A new process-related impurity and an oxidative degradation impurity in erdosteine bulk drug were isolated and identified.
厄多司坦是一种黏液溶解药物，具有抗氧化活性。
本研究旨在建立一种高效液相色谱法，用于测定厄多司坦原料药中厄多司坦及其杂质，并鉴定主要杂质，以帮助提高厄多司坦原料药的质量。
采用CAPCELL PAK C18柱（250 mm×4.6 mm内径，5μm）进行色谱分离。以乙腈-0.01 mol/L柠檬酸溶液（体积比为13 + 87），流速1.0 mL/min作为流动相。检测波长为254 nm。分别通过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，然后通过半制备高效液相色谱法进行纯化。最后，通过多种光谱数据（质谱、1H核磁共振和13C核磁共振）鉴定其结构。
观察到厄多司坦及其相关杂质的良好分离效果。一种新杂质被确认为乙基{2-氧代-2-[(2-氧代四氢-3-噻吩基)氨基]乙基}硫烷基乙酸酯，即厄多司坦乙酯，是在使用乙醇作为精制溶剂的厄多司坦原料药精制过程中产生的。另一种杂质被确认为{2-氧代-2-[(2-氧代四氢-3-噻吩基)氨基]乙基}亚磺酰基乙酸，即厄多司坦氧化物。
建立并验证了一种测定厄多司坦及其相关杂质的高效液相色谱法。分离并鉴定了厄多司坦原料药中的两种主要杂质。避免使用乙醇作为精制溶剂可提高厄多司坦原料药的纯度。
分离并鉴定了厄多司坦原料药中一种新的工艺相关杂质和一种氧化降解杂质。
