UPLC-MS/MS法同时测定复方半夏片中吡咯里西啶生物碱和马兜铃酸的含量及风险评估  

Simultaneous Determination of Pyrrolizidine Alkaloids and Aristolochic Acids in Fufang Banxia Tablets by UPLC-MS/MS and Risk Assessment

作　　者：谭春梅 方翠芬 王娟娟 董婷 张琳琳 郑成 陈碧莲 TAN Chunmei;FANG Cuifen;WANG Juanjuan;DONG Ting;ZHANG Linlin;ZHENG Cheng;CHEN Bilian(NMPA Key Laboratory for Quality Evaluation of Traditional Chinese Medicine(Traditional Chinese Patent Medicine),Zhejiang Institute for Food and Drug Control,Hangzhou 310052,China)

机构地区：[1]浙江省食品药品检验研究院,国家药品监督管理局中成药质量评价重点实验室,杭州310052

出　　处：《中国药学杂志》2024年第17期1637-1642,共6页Chinese Pharmaceutical Journal

摘　　要：目的建立超高效液相色谱-串联质谱(UPLC-MS/MS)联用同时测定复方半夏片中3个吡咯里西啶生物碱和5个马兜铃酸的测定方法,并进行初步的风险评估。方法ACQUITY UPLC BEH C18色谱柱(2.1 mm×100 mm,1.7μm),以甲醇-乙腈(1∶1)的混合溶液为流动相A,以含体积分数0.1%甲酸溶液和5 mmol·L^(-1)甲酸铵为流动相B,梯度洗脱,流速为0.3 mL·min^(-1),柱温为30℃,采用电喷雾离子源(ESI),多反应监测模式(MRM),正离子扫描。结果3个吡咯里西啶在0.48~482.60 pg内线性关系良好,5个马兜铃酸在0.51~538.51 pg内线性关系良好,相关系数均大于0.99;平均回收率为60.4%~120.5%,相对标准偏差(RSD)为2.1%~9.7%;5批样品中均检出吡咯里西啶生物碱和马兜铃酸,阳性样品吡咯里西啶生物碱总含量为5.42~5.46 mg·kg^(-1),马兜铃酸总含量为1.04~1.70 mg·kg^(-1)。结论建立的方法操作简便、准确,可同时测定复方半夏片中3个吡咯里西啶生物碱和5个马兜铃酸的含量;初步的风险评估显示,复方半夏片的安全风险较低。OBJECTIVE To establish an ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for simultaneous determination of three pyrrolizidine alkaloids and five aristolochic acids in Fufang Banxia Tablets,and carry out preliminary risk assessment.METHODS ACQUITY UPLC BEH C18 column(2.1 mm×100 mm,1.7μm)was used.The mixed solution of methanol-acetonitrile(1∶1)was used as mobile phase A,and 0.1%formic acid solution and 5 mmol·L^(-1)ammonium formate were used as mobile phase B.Gradient elution was performed at a flow rate of 0.3 mL·min^(-1)and the column temperature was maintainedat 30℃.Electrospray ion source(ESI),multiple reaction monitoring mode(MRM)and positive ion scanning were used.RESULTS Three pyrrolizidine alkaloids showed a good linear relationship in the range of 0.48-482.60 pg,and five aristolochic acids showed a good linear relationship in the range of 0.51-538.51 pg.The correlation coefficients were higher than 0.99.The average recoveries were between 60.4%%and 120.5%,with RSDs of 2.1%-9.7%.Pyrrolizidine alkaloids and aristolochic acids were detected in all five batches,the total content of pyrrolizidine alkaloids was 5.42-5.46 mg·kg^(-1),and the total content of aristolochic acids in positive samples were 1.04-1.70 mg·kg^(-1).CONCLUSION The established method is simple and accurate,and can simultaneously determine the contents of three pyrrolizidine alkaloids and five aristolochic acids in Fufang Banxia Tablets.The preliminary risk assessment shows that the safety risk of Fufang Banxia Tablets is low.

关 键 词：复方半夏片 吡咯里西啶生物碱 马兜铃酸 超高效液相色谱-串联质谱 含量测定 风险评估 

分 类 号：R917[医药卫生—药物分析学]