Elemental Impurities

Manufacturers of pharmaceutical drugs must follow the guidelines for testing for elemental impurities in USP 232 and 233, which have been harmonized with ICH Q3D guidelines around the world. The USP and ICH elemental impurities testing guidance support a risk-based approach for the evaluation and control of elemental impurities in drug products or permitted daily exposures (PDE) for individual elements. This is done to make sure that toxic metals are not used in the manufacturing process.

Element impurities in drug products can come from a number of places. For example, they could be leftover catalysts that were added on purpose during synthesis, or they could be there naturally. Some of the things that can be used as sources are manufacturing equipment, solvents, water, and reagents. If there is no therapeutic benefit for patients, their levels in excipients, drug substances, drug products, and dietary supplements should be kept within acceptable limits. The ICH Q3D guidelines, which are now in sync with compendia, make it clear what is needed.

With decades of experience in both chemical analysis and regulatory issues, we provide industry-leading, highly accurate element-specific protocols, advanced analytical method development, and validation in accordance with USP 232, 233, and ICH Q3D guidelines for testing elemental impurities in drug products, down to the necessary trace level limits of detection.

With the most advanced ICP-OES and ICP-MS instruments in our laboratories and teams of dedicated and experienced scientists, as well as a proven track record of developing and validating customized, specific elemental impurities methods, protocols, and study designs for challenging APIs and complex sample matrices with accurate trace level detection, including those with low solubility, we can meet your product testing needs. Our deep knowledge of USP heavy metals testing and elemental impurities testing of biologics and pharmaceuticals, along with a number of advanced techniques like ICP-MS, individualized sample preparation methods, and the use of three collision gases, make it possible to find low levels of elements that are usually hidden by polyatomic interferences (e.g., sulfur and silicon).

We offer GMP-compliant elemental impurities analysis of pharmaceutical products, ingredients, active pharmaceutical ingredients (APIs), and other health products. Our facilities have some of the most sensitive tools available, and our metals analysis experts have decades of experience. Typical limits of quantification are much lower than typical PDE requirements, with some reaching ppt (parts per trillion) levels with as little as 10 mg of sample weight. Our facilities offer a full range of services, from initial scans to help with pre-risk assessment to full and thorough ICH method validation. Because we have a lot of experience, we can manage each product and project in an open way that involves everyone.

We make sure that elemental impurities in small and large molecule drug products are under control by having a deep understanding of regulatory requirements, a consultative approach, a well-equipped lab, and a track record of finding the best methods for complex and difficult samples. Our end-to-end solutions include regulatory-driven elemental impurities risk assessment support, screening, batch-to-batch testing, raw material testing, method development, validation, and optimization, and elemental impurities USP 232/233 and FDA ICH Q3D testing programs. We use analytical techniques that give the most accurate results down to trace levels and a customized approach to method development.


  • Elemental impurity testing per ICH Q3D and USP <232> or <233>
  • Method development and validation
  • Limit test validation
  • Semi-quantitative screening
  • Trace metal analysis
  • Targeted metals analysis
  • Monograph (compendial) testing
  • Extractables and leachables studies
  • Raw materials testing
  • Finished product testing
  • Batch and lot release testing
  • Metal speciation
  • Impurity characterization
  • Elemental impurities sample preparation techniques

To discuss how Synergy Bioscience can help you, please contact us