微波消解ICP-MS法对活血止痛软胶囊、片、胶囊中30种重金属及无机元素分析

Analysis of 30 Heavy Metals and Inorganic Elements in Huoxue Zhitong Soft Capsules, Tablets and Capsules Based on Microwave Digestion ICP-MS

目的:应用电感耦合等离子体质谱技术(ICP-MS)建立同时测定活血止痛制剂(胶囊、片剂、软胶囊)中30种无机元素的方法,并合理评价。方法:样品采用程序升温微波消解处理(胶囊剂47批,片剂29批,软胶囊7批),通过在线内标法以元素72锗(Ge)、115铟(In)、209铋(Bi)为内标,电感耦合等离子体质谱法测定。结果:钠(Na)、镁(Mg)、钾(K)、钙(Ca)、铝(Al)元素检测质量浓度线性范围为0.2~20μg/mL,汞(Hg)元素检测质量浓度线性范围为0.2~10 ng/mL,铁(Fe)元素检测质量浓度线性范围为0.8~80μg/mL,镉(Cd)、铅(Pb)、砷(As)、钴(Co)、钒(V)、镍(Ni)、铊(Tl)、金(Au)、钯(Pd)、铱(Ir)、锇(Os)、铑(Rh)、钌(Ru)、硒(Se)、银(Ag)、铂(Pt)、锂(Li)、锑(Sb)、钡(Ba)、钼(Mo)、铜(Cu)、锡(Sn)、铬(Cr)元素检测质量浓度线性范围为0.5~300 ng/mL(r均大于0.998)。回收率为88.3%~120.4%,RSD为0.9%~5.9%。制剂中Ca、Na、K、Fe等人体有益元素显著高于其他无机元素,另参照现行药典标准中活血止痛胶囊Pb、As、Hg重金属限度综合评价,其胶囊剂和软胶囊中Pb、As、Hg元素残留量符合相关限度要求,6批片剂中Pb超出以上限度,存在一定用药安全隐患。结论:该方法操作简便、灵敏、准确,可用于活血止痛制剂中多元素检测,为元素风险监控及质量评价提供技术参考。

Objective To establish a method for simultaneous determination of 30 elements in Huoxue Zhitong preparations(capsules, tablets and soft capsules) by inductively coupled plasma mass spectrometry(ICP-MS). Methods Samples(47 batches of capsules, 29 batches of tablets, 7 batches of soft capsules) were treated with temperature programmed microwave digestion. Germanium, indium and bismuth were used as internal standards by on-line internal standard method and determined by inductively coupled plasma mass spectrometry(ICP-MS). Results The linear range of detection concentration of Na, Mg, K, Ca and Al was 0.2-20 μg/mL. The linear range of Hg was 0.2-10 ng/mL, and the linear range of Fe was 0.8-80 μg/mL. The linear range of Cd, Pb, As, Co, V, Ni, Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag, Pt, Li, Sb, Ba, Mo, Cu, Sn and Cr was 0.5-300 ng/mL(all r>0.998). The recoveries of elements were between 88.3% and 120.4% with RSD 0.9% to 5.9%. Ca, Na, K, Fe and other beneficial elements in the preparation were significantly higher than those of other inorganic elements. According to the comprehensive evaluation of heavy metal limits of Pb, As and Hg in Huoxue Zhitong capsules in current Pharmacopoeia standards, the residues of Pb, As and Hg in capsules and soft capsules met the relevant limits, but Pb in 6 batches of tablets exceeded the above limits, so there was some hidden danger in drug use. Conclusion the method is simple, sensitive and accurate, can be used for the determination of multi-elements in Huoxue Zhitong preparation, and provides technical reference for element risk monitoring and quality evaluation.