目的: 采用色谱-质谱联用技术鉴定黄体酮阴道缓释凝胶中的有关物质。方法: 采用YMC-Triart C18（150 mm×4.6 mm,3 μm）色谱柱,以乙腈-水为流动相梯度洗脱,对黄体酮阴道缓释凝胶有关物质进行分离,电喷雾正离子化-四极杆-飞行时间串联质谱（ESI Q TOF MS）在5~45 eV碰撞能下高分辨测定各有关物质母离子及其子离子的准确质量和元素组成,并解析鉴定有关物质的结构。结果: 在所建立的分析条件下,黄体酮及其有关物质分离良好,检测并鉴定出黄体酮阴道缓释凝胶及其强制降解试验样品中18个主要有关物质,其中7个为EP或已知杂质,而其他均为本研究首次鉴定出的未知有关物质。色谱-质谱联用技术能有效地分离鉴定黄体酮阴道缓释凝胶中的有关物质。结论: 黄体酮在酸、碱、高温干法强制降解条件下不稳定,且易形成氧化降解产物,研究结果可为黄体酮阴道缓释凝胶质量控制提供参考依据。
Objective: To identify the related substances of progesterone sustained-release vaginal gel by liquid chromatography mass spectrometry (LC-MS). Methods: The separation was carried out on YMC-Triart C18 (150 mm×4.6 mm, 3 μm) column by gradient elution using acetonitrile and water as the mobile phases. The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry (ESI Q TOF MS) at collision energies of 5-45 eV. The structures of the related substances were identified by spectral analysis. Results: Under the established analytical condition, progesterone and its related substances were adequately separated, and 18 major related substances were detected and identified by hyphenated techniques in progesterone sustained-release vaginal gel and their stressed samples. Among them, 7 were the impurities listed in the EP or previous reported, and the others were unknown related substances identified for the first time in this paper. The established LC-MS technique was effective for the separation and identification of the related substances of progesterone sustained-release vaginal gel. Conclusion: Progesterone is unstable under acid, alkaline, and high-temperature stress conditions, and prone to produce oxidation degradants. The research results can provide a reference for the quality control of progesterone sustained-release vaginal gel.
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