保健酒及酒类制品中非法添加PDE-5抑制剂及其衍生物的监测及结果分析

Investigation and analysis of the PDE-5 inhibitors and their analogues in tonic wines and wine products

目的:对保健酒及酒类制品中非法添加磷酸二酯酶(PDE-5)抑制剂及其衍生物进行监测,并对监测结果进行分析讨论。方法:参照"国家食品药品监督管理局药品检验补充检验方法和检验项目批准件(编号2009030)方法。LC-MS/MS法条件:采用Shim-pack XR-ODS(100 mm×2.0 mm,2.2μm)色谱柱,以0.1%乙酸的10 mmol·L^(-1)乙酸铵溶液(A)-乙腈(B)为流动相,梯度洗脱(0~8 min,27%B;8~18 min,27%B→80%B,18~20 min,80%B),流速0.3 m L·min^(-1);采用电喷雾离子源(ESI),正离子扫描模式,一级质谱全扫描范围为m/z 100~1 000,二级质谱全扫描范围为m/z 40~1 000。HPLC法条件:采用Inertsil ODS-SP C18(4.6 mm×150 mm,5μm)色谱柱,以10 mmol·L^(-1)乙酸铵溶液(A)-甲醇(B)-乙腈(C)为流动相,梯度洗脱(0~15 min,10%B→25%B;15~25 min,25%B→55%B;25~35 min,55%B,保持15%C),流速1.0 m L·min^(-1),柱温为室温,二极管阵列检测器,扫描范围为200~400 nm。结果:64批次样品中12批次检测到PDE-5抑制剂及其衍生物,其中检出批件中涉及的西地那非、伐地那非、氨基他达拉非和羟基豪莫西地那非4种非法添加成分。另外检出5种批件中未涉及的PDE-5抑制剂衍生物,为丙氧基苯基艾地那非、丙氧基苯基硫代艾地那非、艾地那非和羟基硫代豪莫西地那非,且有一种未见报道的新型PDE-5抑制剂衍生物(暂无命名)。结论:保健酒及酒类制品中检出非法添加PDE-5抑制剂及其衍生物,需建立快速有效的针对新型PDE-5衍生物的监测方法,并加强对相关销售渠道的监管,保障人民生命健康。

Objective：To supervise the PDE-5 inhibitors and analogues in tonic wines and wine products and then analyze the result.Methods：The supplement standard of the drugs from SFDA（No.2009030）was taken as reference.LC-MS/MS analysis was carried out on a Shim-pack XR-ODS column（100 mm×2.0 mm,2.2 μm）with mobile phase at a flow rate of 0.3 m L·min^-1.The mobile phase consisted of 10 mmol·L^（-1） ammonium acetate containing 0.1% acetic acid（A）and acetonitrile（B）,and the ratios of B were 0-8 min,27%B;8^（-1）8 min,27%B → 80%B,and 18-20 min,80%B.ESI in positive electrospray ion was used with the 100（-1） 000 MS and 40（-1） 000 MS/MS scan ranges.HPLC analysis was carried out on an Inertsil ODS-SP C18 column（4.6 mm×150 mm,5 μm）with mobile phase at a flow rate of 1.0 m L·min^-1.The mobile phase consisted of 10 mmol·L（-1） ammonium acetate（A）,methanol（B）and acetonitrile（C）,and the ratios of B were 0（-1）5 min,10%B → 25%B;15-25 min,25%B → 55%B,25-35 min,55%B and the ratio of C was kept at 15%.The column temperature was room temperature,and the DAD scan range was from 200 to 400 nm.Results：The PDE-5 inhibitors and analogues were found in about 12 batches among a total of 64 batches of samples.Except for sildenafil,vardenafil,aminotadalafil and hydroxyhomosildenafil reported in the document,five new PDE-5 inhibitor analogues were detected,including propoxyphenyl aildenafil,propoxyphenyl thioaildenafil,aildenafil and hydroxyhomosildenafil,which are not mentioned in the document,among which there was a new compound never being reported before.Conclusion：PDE-5 inhibitors and analogues were inspected in tonic wines and wine products.There is a need to set up effective and rapid detection methods for new PDE-5 inhibitor analogues,and strengthen the supervision to protect the health of people.