HEAVY METAL TESTING

Metallic impurities in pharmaceutical substances or drug products may originate from several sources like raw materials, metal catalysts or metal reagents used during synthesis, manufacturing equipment and piping, bulk packaging, the environment, cleaning solvents etc. Heavy metals most often implicated in human poisoning are lead, mercury, arsenic, and cadmium. Some heavy metals such as zinc, copper, chromium, iron, and manganese, are required by the body in small amounts, but these same elements can be toxic in higher quantities. The content of heavy metals in pharmaceutical substances is tested to control and quantify the levels of metals as a group due to the toxicity of the elements, and also due to the reason that heavy metal residue is a general marker for the quality of the product. The specification for heavy metals in active pharmaceutical ingredients is set, taking into account its route of administration, maximum daily dosage, typical duration of intake and risk assessment.

Heavy metals are largely found in nature as minerals and ores. They get into the environment as a result of being extracted, from erosion or from volcanic activity. Heavy metals are used in a number of technical applications and processes and can get into the environment or into products unintentionally.

Intake of heavy metals occurs in the growth process of plants by absorption from water, from the ground and by aerosols from the ambient air. Contamination can also occur from the spillage of pesticides or sewage sludge containing heavy metal.

In the manufacturing of pharmaceutical products, catalysts containing heavy metals are often involved in the synthesis. Heavy metals can also transfer into the process by abrasion or by leaching (e.g. Fe, Ti, Cu, Cr and so on.) If they are not removed efficiently, then the tainted products could get into the market.

To be measured, solid matter samples must be present in a dissolved form (most commonly in aqueous solution). Digestion nearly always involves additional dilution of the sample and this makes even lower detection limits necessary. Matrix-destroying methods reduce interference caused by the matrix during measurement.

The following digestions are commonly used, depending on the matrix and the sample.

  • Dissolving in aqueous solution (mostly acidified)
  • Dissolving in an organic solvent
  • Extraction