盐酸左西替利嗪片有关物质的色谱-质谱结构鉴定

发布时间：2018-01-27 15:20

本文关键词：盐酸左西替利嗪有关物质结构鉴定未知杂质杂质二级质谱裂解途径乳糖乙醇 LC-Triple TOF/MS -[-[(-氯苯基)(苯基)甲基]哌嗪--基]乙酸 -[-[-[(-氯--羟基苯基)(苯基)甲基]哌嗪--基]乙氧基]乙酸( R)--[-[(-氯苯基)(苯　出处：《药物分析杂志》2017年02期 　论文类型：期刊论文

【摘要】：目的:采用LC-MS技术对盐酸左西替利嗪片中有关物质进行结构鉴定。方法:采用Welch Xtimate C18色谱柱(250 mm×4.6 mm,5μm),以甲醇-四氢呋喃-磷酸盐溶液(磷酸二氢钠3.1 g,用水溶解稀释至1 000 mL,用磷酸调节pH至2.9)(44.5∶5.5∶50)为流动相等度洗脱,对盐酸左西替利嗪片中有关物质进行分离;应用Kinetex C18(100 mm×n2.1 mm,1.7μm)色谱柱,以水(含0.05%甲酸)-甲醇(含0.05%甲酸)流动相梯度洗脱,采用色谱-质谱(MS)技术测定离子准确质量并分析离子特征,结合对照品确证有关物质结构;结合处方分析,推测未知杂质结构,并揭示杂质产生的来源。结果:在所建立的条件下,盐酸左西替利嗪与其有关物质分离良好,检测出10个有关物质,并综合分析、鉴定了有关物质结构,推测其中最大的未知杂质为左西替利嗪与残留乙醇酯化生成的2-[2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-基]乙氧基]乙酸乙酯,另2个较大未知杂质为是左西替利嗪的羧基与乳糖不同位置的羟基产生的酯化产物(R)-2-[2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-基]乙氧基]乙酸乳糖酯。结论:本研究为盐酸左西替利嗪片的处方研究及制剂工艺提供指导。
[Abstract]:Objective: to identify the related substances in levatirizine hydrochloride tablets by LC-MS. Methods: Welch Xtimate C18 column was used. 250 mm 脳 4.6 mm. 5 渭 m, methanol-tetrahydrofuran phosphate solution (sodium dihydrogen phosphate 3.1 g) was dissolved and diluted to 1 000 mL with water. The related substances in levocetirizine hydrochloride tablets were separated by phosphoric acid to adjust pH to 4.05: 5.5: 50) as flow equal degree elution. A Kinetex C18 ~ (18) 100 mm 脳 n ~ (2. 1) mm ~ (1.7 渭 m) column was used. The mobile phase gradient elution of water (containing 0.05% formic acid and methanol (containing 0.05% formic acid) was used to determine the accurate mass of ions and analyze the ion characteristics by chromatography-mass spectrometry. To confirm the structure of the related substance in combination with the reference substance; Combined with prescription analysis, the unknown impurity structure was inferred and the origin of impurity was revealed. Results: under the established conditions, levocetirizine hydrochloride and its related substances were separated well and 10 related substances were detected. The structure of the related substances was identified, and the largest unknown impurity was estimated to be the 2-, which was formed by the esterification of levo-cetirizine with residual ethanol. [2-. [4-. [4-chlorophenyl (phenyl) methyl] piperazine] ethoxy] ethyl acetate. The other two major unknown impurities are the esterification products of levo-cetirizine carboxyl group and lactose hydroxyl group in different positions. [2-. [4-. [Conclusion: this study provides guidance for the formulation and preparation of levcetirizine hydrochloride tablets.
【作者单位】：湖南省药品检验研究院;
【分类号】：R927;O657.63
【正文快照】： 2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-基]乙酸;2-[2-[4-[(4-氯-3-羟基苯基)(苯基)甲基]哌嗪-1-基]乙氧基]乙酸;(R)-2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-基]乙氧基]乙酸乳糖酯;(R)-2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-基]乙氧基]乙酸乳糖酯;2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-

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