摘要
通过气相色谱-质谱联用(GC-MS)法,测定奥美沙坦酯原料药中基毒杂质4-氯甲基-5-甲基-1,3-二氧杂环戊烯-2-酮(4-(chloromethyl)-5-methyl-1,3-dioxol-2-one,DMDO-Cl)。选用4,5-二甲基-1,3-二氧杂环戊烯-2-酮(DMDO)为内标物,奥美沙坦酯原料药经1%甲酸的二氯甲烷溶解后,加入正庚烷使奥美沙坦酯析出。取上述清液,用DB-624色谱柱(30m×0.32mm×1.8μm)分离,使用氦气为载气,流速2mL/min,分流比1∶1,程序升温模式,进行测定。用电子轰击(EI)质谱,在离子选择(SIM)模式下,监控m/z 113与m/z 114离子进行检测,测定痕量DMDO-Cl。研究记过表明,该检查方法具有重现性好、灵敏度高、准确可靠的特点。
A gas chromatograph-mass spectrometric （GC-MS） method was developed for the determination of 4 - （chloromethyl） - 5-methyl - 1,3-dioxol - 2-ketone, which is classified as genotoxic impurity and may present in Olmesartan medoxomil drug substance （API） in trace level. The 4,5-dimethyl - 1,3-dioxol -2-one （DMDO） is selected as internal standard. In order to avoid matrix interference, the Olmesartan medoxomil test sample was firstly dissolved in-dichloromethane （DCM） with the aid of 1% formic acid, then n-hexane was added to allow the Olmesartan medoxomil to precipitate completely. The supernatant obtained was injected into the DB - 624 column （30m×0. 32mm × 1.8μm） ,and separated by using helium as carrier gas at flow rate of 2mL/min and split ra- tio of 1 ： 1 under temperature programming mode. The detection of the DMDO-C1 was performed by mass spec- trometry （MS） under Single Ion Monitoring （SIM） Mode. Selective ion monitors were set at m/z 113 for DM- DO-C1 and m/z 114 for DMDO. The method was proved to be of good reproducibility, high sensitivity, accura-
作者
刘勇军
熊学武
巢燕芳
杨铁金
LIU Yong-jun XIONG Xue-wu CHAO Yan-fang YANG Tie-jin(College of Chemistry and Chemical Engineering,Qiqihaer University,Heilongjiang Qiqihaer 161000, Heilongjiang, China HEC Pharm Research and Development Institute, Dongguan 443300, Guangdong, China)
出处
《合成材料老化与应用》
2017年第3期91-95,共5页
Synthetic Materials Aging and Application
关键词
奥美沙坦酯
基因毒性杂质
气质联用
杂质痕量检测
Olmesartan medoxomil
genotoxic impurity
gas chromatograph-mass spectrometry
determination of Impurities at ppm Level
