超高效液相色谱-串联质谱法快速筛查中成药中49种违法添加化学药物

Rapid Determination of 49 Kinds of Illegally-added Chemical Drugs in Chinese Patent Medicine by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

建立了基于超高效液相色谱-串联质谱(UPLC-MS/MS)快速筛查中成药中违法添加8类49种化学药物的方法。样品用乙腈超声提取,采用C 18柱(2.1 mm×100 mm,1.8μm)进行分离,以0.1%甲酸-2 mmol/L乙酸铵水溶液和0.1%甲酸乙腈溶液为流动相梯度洗脱,动态多反应监测(d-MRM)采集模式进行定性和定量检测,外标法定量。结果表明,49种化学药物的线性范围为0~60 ng/mL,相关系数(r^(2))为0.9932~0.9995,检出限为0.290~2.546 ng/g,3个加标水平的回收率为86.4%~107%,相对标准偏差为0.80%~3.5%。采用该方法测定20批实际样品,共检出5批阳性样品,检出的药物为二甲双胍、苯乙双胍、格列苯脲、西地那非、他达拉非和西布曲明,含量分别为0.07697、1.153、0.01341、69500、2400、724.0 mg/kg。该方法具有前处理操作简单、结果准确、灵敏度高等优点,适用于中成药中违法添加化学药物的快速筛查。

An ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed for the rapid screening of 49 kinds of illegally-added chemical drugs divided into eight categories in Chinese patent medicine.The samples were extracted with acetonitrile by ultrasonic extraction,then separated on a C 18 chromatographic column(2.1 mm×100 mm,1.8μm)by gradient elution,with 0.1%formic acid-2 mmol/L ammonium acetate aqueous solution and acetonitrile containing 0.1%formic acid as mobile phases.The qualitative and quantitative analyses were performed under dynamic multiple reaction monitoring(d-MRM)acquisition mode,and external standard method was used for quantitative detection.Results showed that there were linear relationships for 49 drugs in the concentration range of 0-60 ng/mL with their correlation coefficients(r^(2))of 0.9932-0.9995.The limits of detection were in the range of 0.290-2.546 ng/g.Recoveries for the analytes at three spiked levels ranged from 86.4%to 107%,with relative standard deviations of 0.80%-3.5%.Metformin,phenformin,glibenclamide,sildenafil,tadalafil and sibutramine were detected in 5 batches(20 batches in total)of samples,with their detectable amounts of 0.07697,1.153,0.01341,69500,2400,724.0 mg/kg,respectively.With the advantages of simple pretreatment,accurate result and high sensitivity,this method is suitable for the rapid screening of illegally-added chemical drugs in Chinese patent medicine.