Analytical method with ICP-MS for heavy metals as an unintended hazardous material in commercial pharmaceuticals

One major safety issue that has been evident for several years relates to the possible adulteration of traditional medicines with harmful ingredients such as the heavy metals lead, mercury and arsenic. The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. Detection of toxic heavy metals that exceeded Singapore's legal limits in 42 Chinese proprietary medicines was reported. Unintended contamination of heavy metals may be introduced in the finished drug from raw materials and in the process of production and it may be very low level. We developed an analytical method for 9 heavy metals as an unintended hazardous material in commercial pharmaceuticals.

A total of 105 commercial pharmaceuticals were collected, and divided into 5 kinds of formulations, tablet, solution, capsule, cream, patches. All pharmaceutical samples (0.02 ˜ 0.10 g) were prepared by acid digestion with microwave (Mars-X, Agilent) after homogenization. Nine heavy metals (As, Cd, Co, Hg, Mo, Pb, Sb, Se, V) were determined in the pretreated samples with inductively coupled plasma-mass spectrometry (ICP-MS) in the CCT mode.

We tried several pretreatment methods according to the drug formulations and compared the data by the methods. The linearity obtained was very satisfying for analyzing heavy metals, with a coefficient of determination (R²) higher than 0.99. The limits of detection were 1˜10 ng/g sample. The accuracies were 80% to 120% and precisions were lower than 20% RSD. Some heavy metals were identified in a few pharmaceuticals and the concentrations of heavy metals were varied depending on the formulation and efficacy of samples. Further investigation is necessary to identify source and reduce the unintended heavy metals in pharmaceuticals.