UHPLC-MS/MS法测定盐酸普萘洛尔缓释片中基因毒性杂质N-亚硝基普萘洛尔  

Determination of genotoxic impurity N-nitroso-propranolol in Propranolol Hydrochloride Sustained-release Tablets by UHPLC-MS/MS

作　　者：黄海伟[1] 袁松[1] 张娜[1] 张龙浩 刘阳[1] 张庆生[1] HUANG Haiwei;YUAN Song;ZHANG Na;ZHANG Longhao;LIU Yang;ZHANG Qingsheng(NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,National Institute for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院,国家药品监督管理局化学药品质量研究与评价重点实验室,北京102629

出　　处：《药学研究》2023年第7期481-484,共4页Journal of Pharmaceutical Research

基　　金：中国食品药品检定研究院关键技术研究基金(No.GJJS-2022-4-1)。

摘　　要：目的建立盐酸普萘洛尔缓释片中基因毒性杂质N-亚硝基普萘洛尔的超高效液相色谱-串联质谱(UHPLC-MS/MS)检测方法。方法Waters ACQUITY UPLC CSH TM C 18色谱柱(3.0 mm×150 mm,1.7μm),10 mmol·L^(-1)甲酸铵的水溶液(含0.1%甲酸)作为流动相A,乙腈溶液(含0.1%甲酸)作为流动相B,梯度洗脱,流速为0.5 mL·min^(-1),柱温为50℃,进样器温度为5℃,进样体积为10μL,采用多反应监测(MRM)模式,对盐酸普萘洛尔缓释片中的N-亚硝基普萘洛尔进行定量检测。结果N-亚硝基普萘洛尔在1~20 ng·mL^(-1)范围内具有良好的线性关系。低、中、高3个浓度的加样回收率(n=3)在98.4%~103.2%之间,RSD≤2.7%。检测限和定量限分别为0.09 ng·mL^(-1)和0.3 ng·mL^(-1)。检出盐酸普萘洛尔缓释片中基因毒性杂质N-亚硝基普萘洛尔含量为1.8μg·g^(-1)。结论该方法灵敏度高、专属性强,可用于测定盐酸普萘洛尔缓释片中的N-亚硝基普萘洛尔,为盐酸普萘洛尔缓释片的质量控制提供参考。Objective To establish an UHPLC-MS/MS method for determination of N-nitroso-propranolol in Propranolol Hydrochloride Sustained-release Tablets.Methods The separation of N-nitroso-propranolol was performed on a Waters ACQUITY UPLC CSH TM C 18 column(150 mm×3.0 mm,1.7μm)with 10 mmol·L^(-1)ammonium formate aqueous solution(containing 0.1%formic acid)as mobile phase A and acetonitrile solution(containing 0.1%formic acid)as mobile phase B under a gradient elution at a flow rate of 0.5 mL·min^(-1)and a column temperature of 50℃.Multiple reaction monitoring(MRM)was performed on a triple quadrupole mass spectrometer in positive mode.Results The calibration curves was in good linearity in the range of 1~20 ng·mL^(-1).The recoveries(n=3)at low,middle and high spiked concentrations were within 98.4%~103.2%with RSD under 2.7%.The limit of detection was 0.09 ng·mL^(-1),and the limit of quantification was 0.3 ng·mL^(-1).Using the developed method,we detected the N-nitroso-propranolol in Propranolol Hydrochloride Sustained-release Tablets was 1.8μg·g^(-1).Conclusion The method was sensitive and accurate,which can be applied for the quantifications of N-nitroso-propranolol in Propranolol Hydrochloride Sustained-release Tablets,providing reference for quality control of Propranolol Hydrochloride Sustained Release tablets.

关 键 词：N-亚硝基普萘洛尔 基因毒杂质 盐酸普萘洛尔缓释片 含量测定 超高效液相色谱-串联质谱 

分 类 号：R927.1[医药卫生—药学]