丙酸倍氯米松吸入气雾剂中新杂质的定性定量分析

Qualitative and quantitative determination of a new impurity from beclomethasone propionate inhalation aerasol

目的建立丙酸倍氯米松吸入气雾剂中一种新杂质的定性鉴别与定量测定的方法。方法基于超高效液相色谱仪-四极杆静电场轨道阱质谱(UPLC-QE-MS)技术结合Discovery Studio软件对丙酸倍氯米松吸入气雾剂中的新杂质进行鉴别与毒性预测,同时采用UPLC法对该物质进行含量测定。结果丙酸倍氯米松吸入气雾剂中的新杂质为环对苯二甲酸丁二醇酯(PBT)二聚体,Discovery Studio软件预测PBT二聚体有潜在发育毒性、无致突变性、无眼部和皮肤刺激性、无啮齿动物致癌性。9批市售丙酸倍氯米松吸入气雾剂中PBT二聚体的含量范围为每瓶20.5~116.6μg。结论本研究可实现对制剂中新杂质的快速鉴别与毒性预测,同时通过对其进行含量测定,为制剂的质量控制提供一定的理论基础。

Objective To establish a method to qualitatively identify and quantitatively determine a new impurity from beclomethasone propionate inhalation aerasol.Methods Ultraperformance liquid chromatography-Q-exactive orbitrap-mass spectrometry(UPLC-QE-MS)technology and Discovery Studio software were used to identify and predict the toxicity of a new impurity in beclomethasone propionate inhalation aerasol,and the content of this new impurity was determined by UPLC.Results The new impurity in beclomethasone propionate inhalation aerasol was polybutylene terephthalate(PBT)cyclic dimer.Discovery Studio software predicted that PBT dimer had potential developmental toxicity,with no mutagenicity,no ocular and skin irritancy and no rodent carcinogenicity.The content range of PBT dimer in 9 batches of beclomethasone propionate inhalation aerasol was 20.5-116.6μg per bottle.Conclusion This study can realize the rapid identification and toxicity prediction of the new impurity in the preparation,and provide a theoretical basis for the quality control of the preparation by determining their content.