Elemental Impurities per USP <232> and <233> by ICP-MS

Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)

Inductively coupled plasma-mass spectrometry (ICP-MS) is a powerful tool for analyzing trace metals in pharmaceuticals samples. A large range of elements can be detected using an ICP-MS. Inorganic impurities in pharmaceutical, biological samples have been measured according to the USP <231> colorimetric method. The USP <231> method is limited in that it cannot distinguish between each metal and does not give individual concentrations. To address these limitations, modern instrument like the ICP-MS has been recommended as a replacement to determine heavy metals concentrations, and the USP has created new monograph for heavy metals USP<232> and <233>. Because elemental impurities pose toxicological concerns and do not provide any therapeutic benefit to the patient, their levels in drug products should be controlled within acceptable limits. In general, FDA anticipates that most approved drug products marketed in the United States do not contain any elemental impurities that exceed the Permitted Daily Exposures (PDEs) described in the US Pharmacopeia General Chapter < 232> and ICH Q3D. Upon implementation of General Chapters <232> and <233>, all new NDAs and ANDAs for drug products with an official USP monograph will be expected to meet the requirements for control of elemental impurities described in general chapters <232> and <233>.

Whitehouse Labs offers testing services catering to both USP <232> and <233> chapters. Our objective is to help you determine the testing requirement for your raw materials and finished products so that you will be able to plan ahead for your products.

All of our ICP-MS systems are in compliance with the code of federal regulations 21CFR Part 11. We are now capable of testing Highly Potent Substances with the introduction of our brand new LABConco Xpert Weigh Box laminar flow hood.

Testing expertise

  • Pharmaceutical drug products,
  • APIs, excipients, drug substances
  • Drug products: Oral, Inhalation, Parenteral
  • Raw materials and Reagents
  • Packaging and Container/Closure systems

Elemental Impurities Testing Needs? Leave it to Us

Elemental impurities are the traces of metals that can be found in raw materials or finished drug products.

Potential Source of Elemental Impurities

Elemental impurities in drug products may arise from several sources: through interactions with processing equipment or container/closure systems, by being present in the components of the drug product, or can be present as residual catalysts that were added intentionally to the drug product.

USP <232>/<233> and ICH Q3D

  • ICH Guidance for industry Q3D Elemental impurities contains recommendations for manufacturers of human drugs and biologics by applying a risk based approach to control elemental impurities and PDEs.
  • USP introduced new limits and analytical procedures for elemental impurities in general chapters <232> Elemental Impurities- Limits and <233> Elemental impurities- Procedures.

Elemental Classification Based On Toxicity

After extensive toxicological study, elements are classified as follows:

  • Class 1 (As, Cd, Hg, Pb) –
    Human toxicants with limited or no use in pharmaceutical manufacturing
  • Class 2
    (Toxicity varies based on route of administration)

    • Class 2A (Co, Ni, V)
      Relatively high probability of occurrence in the drug product
    • Class 2B (Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se, Tl)
      Relatively low probability of occurrence in the drug product
  • Class 3 (Ba, Cr, Cu, Li, Mo, Sb, Sn)
    Relatively low toxicity (high limits of Permitted daily exposure)
  • Other elements may be considered to include: Al, B, Ca, Fe, K, Mg, Mn, Na and Zinc.