盐酸西替利嗪片有关物质分析

目的：研究盐酸西替利嗪片的有关物质，探讨生产工艺存在的问题，为提高药品质量提供参考。方法：对18家企业生产的盐酸西替利嗪片，以HPLC法进行有关物质检查，对主要杂质进行定性定量研究，色谱条件：采用CAPCELL PAK C₁₈（4.6 mm×250 mm，5 μm）色谱柱，以0.2%四丁基硫酸氢铵与0.3%一水合磷酸二氢钠溶液（用1 mol·L^-1氢氧化钠调pH至2.8±0.05）和甲醇为流动相，梯度洗脱，检测波长为232 nm。对其中的未知杂质经分离制备后，采用色谱-质谱（MSⁿ）技术测定离子准确质量并分析离子特征，确证有关物质结构；建立原辅料相容性试验确定杂质的产生途径。结果：盐酸西替利嗪中可能存在10个杂质，18家企业的盐酸西替利嗪片中检出的主要杂质为西替利嗪乙酯与西替利嗪乳糖酯，其含量与盐酸西替利嗪片的处方工艺高度相关。结论：目前国产盐酸西替利嗪片的处方工艺不合理，活性成分与辅料不相容。应从处方设计和改造入手，控制盐酸西替利嗪片的有关物质，提高本品质量疗效和临床用药安全。

Objective: To analyze the impurities in cetirizine hydrochloride tablets,and discuss the existing problems of the production process;and provide a reference for improvement of the product quality. Methods: The related substances of 18 manufacturevs' cetirizine hydrochloride tablets were determined by HPLC. The main impurities were studied qualitatively and quantitatively. The chromatographic separation was performed on a CAPCELL PAK C₁₈ column (4.6 mm×250 mm,5 μm) with a mixture of 0.2% tetrabutylammonium bisulfate and 0.3% sodium dihydrogen phosphate monohydrate solution (1 mol·L^-1 sodium hydroxide adjusted to pH 2.8±0.05) -methanol as mobile phase by gradient elution.Detection wavelength was set at 232 nm. After separation and preparation of unknown impurities,the accurate mass of ions was determined by chromatography-mass spectrometry (MSⁿ),and the ion characteristics were analyzed. The structures of impuritis were confirmed with reference substance. The compatibility test between raw materials and pharmaceutical excipients was established to determine the pathway of impurities. Results: There may be 10 impurities in cetirizine hydrochloride. The two main related substances detected in cetirizine hydrochloride tablets from 18 enterprises are cetirizine ethyl ester and cetirizine lactose ester. The content of impurities was highly related to the formulation process. Conclusion: The formulation technology of cetirizine hydrochloride tablets from domestic enterprises is unreasonable,and the active ingredients are incompatible with excipients. The related substances of cetirizine hydrochloride tablets should be controlled from formulation design and modification to improve the quality and clinical medication safety.

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