盐酸西替利嗪口服溶液的有关物质分析

Analysis of Related Substances in Cetirizine Hydrochloride Oral Solution

关键词:  盐酸西替利嗪口服溶液  有关物质  西替利嗪甘油酯  西替利嗪丙二醇酯  质量控制

Key words:  cetirizine hydrochloride oral solution  related substances  cetirizine propylene glycol esters  cetirizine glycerides  quality control

摘要:

目的 通过对盐酸西替利嗪口服溶液的杂质进行分析，探讨生产工艺存在的问题，为提高产品质量提供参考。方法 通过HPLC对3家企业生产的盐酸西替利嗪口服溶液进行有关物质检查，对主要杂质进行定性定量研究。色谱条件： CAPCELL PAK C₁₈ (4.6 mm×250 mm，5 μm)色谱柱，以乙腈-水(17∶83)(用磷酸调节pH值至1.5)和乙腈-水(35∶65)(用磷酸调节pH值至1.5)为流动相，梯度洗脱，检测波长为230 nm。对其中主要杂质采用色谱-质谱联用技术确证结构，通过原辅料相容性试验揭示杂质产生的来源，色谱条件：ACQUITY UPLC HSS-C₁₈(150 mm×2.1 mm，1.7 μm)色谱柱，以20 mmol·L^–1醋酸铵溶液(0.1%乙酸)-甲醇溶液为流动相，梯度洗脱。结果 盐酸西替利嗪口服溶液中可能存在5个杂质，3家企业的盐酸西替利嗪口服溶液中检出的主要杂质为西替利嗪甘油酯(1对非对映异构体)和西替利嗪丙二醇酯(1对非对映异构体)，其产生与盐酸西替利嗪口服溶液的处方工艺高度相关。结论 盐酸西替利嗪口服溶液的处方工艺有待提高，其活性成分与辅料不相容，应从处方设计入手，控制盐酸西替利嗪口服溶液的有关物质，提高本品质量。

Abstract:

OBJECTIVE To analyze the impurities in cetirizine hydrochloride oral solution, and explore the existing problems of the production process, and provide a reference for improvement of the product quality. METHODS The related substances of 3 manufactures’ cetirizine hydrochloride oral solution were determined by HPLC. The main impurities were studied qualitively and quantitatively. The chromatographic separation was performed on a CAPCELL PAK C₁₈ (4.6 mm×250 mm, 5 μm) column with a mixture of acetonitrile-water(17 : 83)(phosphoric acid adjusted to pH 1.5) and acetonitrile-water(35 : 65)(phosphoric acid adjusted to pH 1.5) as mobile phase by gradient elution. Detection wavelength was set at 230 nm. The confirmatory structure of the main impurities was determined by chromatography-mass spectrometry, the compatibility test between raw materials and pharmaceutical excipients was established to determine the pathway of impurities. The chromatographic separation was performed on an ACQUITY UPLC HSS-C₁₈(150 mm×2.1 mm, 1.7 μm) column with 20 mmol·L^–1 ammonium acetate(with 0.1% acetic acid)-methanol as mobile phase by gradient elution. RESULTS There might be 5 impurities in cetirizine hydrochloride oral solution. The two main related substances detected in cetirizine hydrochloride oral solution from 3 enterprises were cetirizine propylene glycol esters(a pair of diastereomers) and cetirizine glycerides(a pair of diastereomers). The emergence of impurities was highly relater to the formulation process. CONCLUSION The formulation technology of cetirizine hydrochloride oral solution need to be improved, and the active ingredients are incompatible with excipients. The related substances of cetirizine hydrochloride oral solution should be controlled from formulation design to improve the quality.