UPLC-MS/MS法确证健儿乐颗粒中的克拉霉素污染

Confirmation of Clarithromycin contamination in Jianerle granules by UPLC-MS/MS

目的采用超高效液相串联质谱法(UPLC-MS/MS)确证微生物限度检查时发现的健儿乐颗粒中的克拉霉素污染。方法按2015年版《中国药典》四部中对WLT、ANB两个生产企业的健儿乐颗粒进行微生物限度检查的计数方法适用性试验时,根据回收率数据结合生产情况推测WLT可能被共线生产品种克拉霉素污染,采用UPLC-MS/MS法确证克拉霉素的污染量。结果ANB公司的健儿乐颗粒1:10供试液即可满足药典规定的试验菌回收率0.5~2.0,WLT公司的需稀释50倍以上方能满足上述要求;采用UPLC-MS/MS法确证WLT公司生产的3批健儿乐颗粒中克拉霉素的污染量,分别为18.9、9.3、6.9μg·g^-1。结论对于微生物限度检查中回收率异常的健儿乐颗粒,UPLC-MS/MS法可快速准确地确证其污染的克拉霉素含量。

OBJECTIVE To confirm Clarithromycin by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)contamination in Jianerle granules(JG)discovered in the progress of microbial limit examination.METHODS Microbial limit suitability test methods of JG were established according to Chinese Pharmacopeia 2015.The UPLC-MS/MS was established for determining the content of Clarithromycin in JG where recovery rate was used to estimate abnormal in microbial limit.RESULTS The recovery rate of total aerobic bacteria for ANB company′s JG(10-fold dilution)is 0.5-2,and recovery rate of total aerobic bacteria for WLT company′s JG(more than 50 times dilution)was 0.5-2.The content of clarithromycin in JG was determined by UPLC-MS/MS.The content of Clarithromycin in WLT company′s 3-batch JG was 18.9,9.3 and 6.9μg·g-1,respectively.CONCLUSION UPLC-MS/MS can quickly and accurately determinate the content of clarified Clarithromycin in the JG,of which the recovery rate is abnormal in microbial limit examination.