Chemistry - Meaning of the Term "Heavy Metals" in CofA?

Solution 1:

You are right heavy metals (as Pb) is a vague term. It is being discouraged and individual analysis should be reported. When someone says "I tried to find a clear standard describing this to no avail", it is a good illustration that not all information is on the webpages. It is worthwhile to search books :-)

I used to think this was an old-school analytical terminology and it turns out to be correct because it is based on classical methods. From the Food Chemicals Codex (ISBN 0-309-08866-6), which is a 1000 paged book, has the following information. Later they describe the tests as well.

Heavy Metals (as Pb)

This test is designed to limit the content of common metallic impurities colored by sulfide ion (Ag, As, Bi, Cd, Cu, Hg, Pb, Sb, Sn) by comparing the color with a standard containing lead (Pb) ion under the specified test conditions. It demonstrates that the test substance is not grossly contaminated by such heavy metals, and within the precision of the test, that it does not exceed the Heavy Metals limit given as determined by concomitant visual comparison with a control solution. In the specified pH range, the optimum concentration of lead (Pb) ion for matching purposes by this method is 20 micrograms in 50 mL of solution. The most common limitation of the Heavy Metals Test is that the color the sulfide ion produces in the Sample Solution depends on the metals present and may not match the color in the Lead Solution used for matching purposes. Lead sulfide is brown, as are Ag, Bi, Cu, Hg, and Sn sulfides. While it is possible that ions not mentioned here may also yield nonmatching colors, among the nine common metallic impurities listed above, the sulfides with different colors are those of As and Cd, which are yellow, and that of Sb, which is orange.

If a yellow or orange color is observed, the following action is indicated: Because this monograph does not include an arsenic requirement, As should be determined. Any As found should not exceed 3 mg/kg. If these criteria are met, Cd may be a contributor to the yellow color, so the Cd content should be determined. If an orange color is observed, the Sb content should be determined. These additional tests are in accord with the section on Trace Impurities in the General Provisions of this book, as follows: ‘‘if other possible impurities may be present, additional tests may be required, and should be applied, as necessary, by the manufacturer, vendor, or user to demonstrate that the substance is suitable for its intended application.’’

Solution 2:

In addition to @M.Farooq answer on the food sector, if you read heavy metals as Pb in a pharmaceutical environment, it stems from a method of the United States Pharmacopoeia, active until 2018 (same for the European, Japanese and British Pharmacopoeia as well as others). Up until then, it was normal to analyse heavy metals as a sum parameter for many drug products. The analysis was a limit test against a lead nitrate standard, where you compare the colour. From the USP chapter 231 of USP 39-NF 34 valid until 1. January 2018 :

This test is provided to demonstrate that the content of metallic impurities that are coloured by sulphide ion, under the specified test conditions, does not exceed the Heavy metals limit specified in the individual monograph in percentage (by weight) of lead in the test substance, as determined by concomitant visual comparison with a control prepared from a Standard Lead Solution. [NOTE—Substances that typically will respond to this test are lead, mercury, bismuth, arsenic antimony, tin, cadmium, silver, copper, and molybdenum.]

In addition for a lot of pharmaceutical products, special analysis for metals used in the manufacturing process were described in their monographs, such as limits of Arsenic, Iron, Lead and others.

Here is an article and a graph of the sensitivy of this method, which was quite bad.

It was a worldwide act and discussion, until finally in 2018 the International Council for Harmonisation (ICH) guidance for industry Q3D Elemental Impurities(ICH Q3D) was set in place and adopted by the regional pharmacopoeias, see FDA USP .

For the European part, here is a short "historic overview" from the European Agency.

Elemental impurities in the Ph. Eur.

The Stone age : from genesis to 2008

  • use of non specific wet chemical test for « heavy metals »
  • limit to 10 or 20 ppm > (with reference to lead)

The Bronze age : from 2008 to 2013

  • EMA GL on the specification limits for residues of metal catalysts or metal reagents

The Golden age : starting 2013

  • CHMP decision to delay the application of the EMA guideline to existing marketed products discussions on the implementation of ICH Q3D guideline

Then the chapter <231> was deleted form the USP and the chapters <232> Elemental Impurities—Limits and <233> Elemental Impurities—Procedures were released.

Now, elemental impurities are analysed by ICP or AAS on an risk based approach, mostly by studying, which elements are used in the manufacturing process, as part of the packaging, colouring etc and can leach into the drug, and then analysing the content.

So, in the pharmaceutical industry, heavy metals as Pb was a specific method for the analysis of heavy metals via colour comparison test. Until 2018, pharmaceutical products could be released with a Heav metal test based on a 1800 or 1900 visual colour comaprison test which excluded a lot of metals. Heavy metals "without Pb" did exist informal as a short version, for metals screenings and to talk about outdated methods.