Heavy Metals Analysis by ICPMS

USP <231> Heavy Metals

The limit test for heavy metals is a qualitative test that demonstrates that the content of metallic impurities that are colored by sulfide ion does not exceed the specified limit. Metals that typically respond to this test are lead, mercury, bismuth, arsenic, antimony, tin, cadmium, silver, copper, and molybdenum.

There are three different sample preparation techniques that can be utilized in this analysis. Method I, II, or III is specified in individual monographs. Method I is used for substances that produce a clear colorless solution. After addition of a sulfide reagent, the color is compared to both a standard as well as a sample spiked at the limit. In Method II the substance is first carbonized by heating with sulfuric acid, then the carbon is burned in a muffle furnace. Metals are then extracted from the residue, and the analysis can proceed free of any organic interference. Method III is a sulfuric and nitric acid digestion method followed by oxidation with peroxide.

The Problem: Sample Size

Sample size for USP<231> is determined by the following formula: 2.0/(1000L), where L is the limit in percentage. Thus for a limit of 0.001% (or 10 ppm), at least 2 g of material is required. This may be impractical for many substances such as proteins or peptides. For this reason, we offer a more sensitive and specific test using ICPMS which requires as little as 10 mg samples.

ICP-MS (Inductively Coupled Plasma-Mass Spectrometry)

While USP<231> does not give a specific result for any of the elements, ICP-MS can identify and quantify each metallic impurity with higher sensitivity. ICP-MS can be used to test for just the heavy metals or practically the whole Periodic Table in one analysis (>60 elements). USP<730> has appeared in the Pharmacopeial Forum to cover such tests.

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ICP-MS, An Alternative

Alternatives to USP<231> include some of the spectroscopic techniques such as GFAA, ICP-OES, and ICP-MS. Of these, ICP-MS is the method of choice.

ICP-MS

is the most sensitive technique, having the lowest detection limits (0.01-1 ug/L in solution),
is a fast, multi-element technique (up to 60 elements in a 2 minute scan)
has definitive, multiple isotope identification (less prone to interferences)

Typical detection limits for ICPMS are 0.01-1 ug/L (ppb) in solution. Sample preparation usually consists of simply diluting the sample in 1% nitric acid although we offer a variety of digestion techniques. Since ICP-MS is the most sensitive technique for trace elements in solution, a 10 mg sample will give detection limits for most elements in the range of 0.01-1 ug/g (ppm). More than 60 elements can be determined in the same analysis which is a big advantage over GFAA where

each element is done separately. We offer a variety of single element, multi-element including just the <231> heavy metals, and complete (>60 element) metals screens.

Some proteins bind metals, and the metal assay is important for QC. Here again, using only very small samples, ICP-MS can accurately assay the metal content.

For a quotation...

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