提出了电感耦合等离子体质谱法(ICP-MS)同时测定六味地黄丸中钠、镁、铝、钾、钙、钒、铬、锰、铁、钴、镍、铜、锌、镓、砷、硒、铷、锶、镉、铯、钡、铊、铅等23种元素的含量,结合化学计量学对各元素含量进行分析,并根据人用药品注册技术要求国际协调会颁布的元素杂质指导原则对镉、铅、砷、钴、钒、镍、铜、铬等8种有害元素进行健康风险评估。六味地黄丸通过微波消解法处理,碰撞池模式下选用⁴⁵Sc作为内标测定²³Na、²⁴Mg、²⁷Al、³⁹K、⁴⁰Ca、⁵¹V、⁵²Cr、⁵⁵Mn、⁵⁶Fe的含量,⁷³Ge作为内标测定⁵⁹Co、⁵⁹Ni、⁶⁴Cu、⁶⁶Zn、⁷⁰Ga、⁷⁵As、⁷⁹Se、⁸⁵Rb、⁸⁸Sr的含量,¹¹⁵In作为内标测定¹¹²Cd、¹³³Cs、¹³⁷Ba的含量,²⁰⁹Bi作为内标测定²⁰⁵Tl、²⁰⁷Pb的含量。结果显示:23种元素的质量浓度在一定范围内与对应的各元素响应值与内标响应值比值呈线性关系,检出限(3s/k)为0.000 9~4.807 μg·L^-1;按照标准加入法进行回收试验,加标回收率为84.9%~112%。根据21批样品测定结果,建立六味地黄丸的元素指纹图谱,利用SPSS 20.0软件进行主成分分析和聚类分析,并对有害元素进行健康风险评估。结果表明:六味地黄丸中23种元素含量具有一定规律,指纹图谱可用于鉴别六味地黄丸;主成分分析得到4个主成分,累计方差贡献率为81.579%,筛选出钒、钴、铯、铁、铊、镓、钡、镁、锶、钠、硒、镉为六味地黄丸的特征元素;聚类分析将21批样品分为3类,大多数样品中元素含量具有相似性;健康风险评估结果显示其中一批样品中铅元素含量存在健康风险,其余批次样品中有害元素健康风险在可接受范围内。

A method for the simultaneous determination of 23 elements, including Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Cd, Cs, Ba, Tl and Pb in Liuwei Dihuang pills by inductively coupled plasma mass spectrometry (ICP-MS) was proposed, and the content of each element was analyzed with chemometrics. According to guideline for elemental impurities issued by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, health risks of 8 harmful elements including Cd, Pb, As, Co, V, Ni, Cu and Cr were evaluated. The Liuwei Dihuang pills were digested by microwave, and ²³Na, ²⁴Mg, ²⁷Al, ³⁹K, ⁴⁰Ca, ⁵¹V, ⁵²Cr, ⁵⁵Mn and ⁵⁶Fe were determined by using ⁴⁵Sc as internal standard with collision pool mode, ⁵⁹Co, ⁵⁹Ni, ⁶⁴Cu, ⁶⁶Zn, ⁷⁰Ga, ⁷⁵As, ⁷⁹Se, ⁸⁵Rb and ⁸⁸Sr by using ⁷³Ge as internal standard, ¹¹²Cd, ¹³³Cs and ¹³⁷Ba by using ¹¹⁵In as internal standard, ²⁰⁵Tl and ²⁰⁷Pb by using ²⁰⁹Bi as internal standard. It was shown that the linear relationships between the mass concentrations of 23 elements and the ratios of corresponding response values of each element to internal standard in definite ranges, with detection limits (3s/k) in the range of 0.000 9-4.807 μg·L^-1. Test for recovery was made by standard addition method, giving results in the range of 84.9%-112%. The fingerprints of elements of Liuwei Dihuang pills were established according to the determination results of 21 batches of samples, and SPSS 20.0 software was used for principal component analysis and cluster analysis, and the health risk assessment of harmful elements was conducted. The results showed that the contents of 23 elements in Liuwei Dihuang pills had certain regularity, and the fingerprints could be used to identify Liuwei Dihuang pills. Four principal components were obtained by principal component analysis, and the cumulative variance contribution rate was 81.579%, and V, Co, Cs, Fe, Tl, Ga, Ba, Mg, Sr, Na, Se and Cd were selected as the characteristic elements of Liuwei Dihuang pills. The 21 batches of samples were divided into 3 categories by cluster analysis, and the contents of elements in most samples were similar. The health risk assessment showed that the content of Pb in one batch of sample presented a health risk, while the health risk of harmful elements in the remaining batch of samples was within the acceptable range.