How to Use XRF to Rapidly Trace Elemental Analysis While Ensuring the Purity of Pharmaceuticals

by Myung-hee Hong, Tuesday, 15th October 2024

Training to become a chemist or a pharmaceutical scientist focuses on learning how to form new chemical bonds. Much of your time is spent learning how to perform reactions designed by chemists of past eras. In the industry, when it comes to making actual molecules for real patients, just as much time (if not more) is spent on molecule purification. This is because developing the best next-generation therapies requires the ability to produce molecules in their pure forms.

It can be said that scaling up for manufacturing and process development research is the most important part.

Determining the Purity of Pharmaceuticals

When developing synthetic processes for pharmaceutical APIs, it’s important to remove elemental impurities related to metal catalysts before downstream processing.

Metal catalysts are the cornerstone of organic chemistry and play critical roles in various chemical transformations. However, when used in pharmaceutical API synthesis, it is important to remove elemental impurities related to these catalysts to ppm levels before downstream processing.

The efficiency of scavenging processes is typically determined using inductively coupled plasma spectroscopy (most commonly ICP-OES or ICP-MS). While ICP is extremely accurate at detecting elemental impurities at very low concentrations, it is a time-consuming and costly process. Waiting for results can delay process development decisions, which could halt the project.

Overcoming the Challenges of ICP

As the cost and risk associated with drug development continue to rise, pharmaceutical scientists need to find innovative ways to improve efficiency at every stage of research and development. And they must do so without compromising on the quality and reliability of analysis, lest they face compliance issues!

Over the years, we have interviewed many pharmaceutical scientists who use ICP. Through these conversations, we have identified several challenges customers face regarding ICP.

Challenges of ICP

  • Feedback loop is slow due to time required for sample preparation
  • Impossible to deploy ICP remotely or at production lines due to required infrastructure and utilities
  • Labor-intensive – ICP requires highly trained dedicated operators
  • Requires the use of hazardous chemicals that are dangerous to users and environmentally harmful
  • High operating costs
  • Difficult to measure halogens
  • Accidents due to chemicals and glassware
  • No inspection tool available

A major recurring problem from this list of issues is sample preparation. Because there are powdered samples that need to be dissolved in a liquid, this is a very tedious and time-consuming process. The process can take 24 to 48 hours depending on the sample, element, and concentration, and if the analysis needs to be outsourced, it can take much longer.

XRF: A Powerful Solution to Ensure the Purity of Pharmaceuticals

X-ray fluorescence (XRF) is a fast, easy-to-use, and deployable tool for screening elemental impurities to support drug synthesis process development. XRF can be employed as a cost-effective and time-efficient means of conducting metal catalyst removal to support drug synthesis process optimization.

To safely manufacture and deliver pharmaceuticals, companies must control patient exposure to toxic elements such as lead (Pb), mercury (Hg), arsenic (As), and cadmium (Cd) within safe limits as part of drug dosage. In response to this need, the International Council for Harmonisation (ICH) has issued the ICH Q3D guidelines on allowable exposure limits for 24 potentially toxic elements in oral, parenteral, and inhaled pharmaceuticals. Compendial guidelines like those provided in the United States Pharmacopeia (USP) and chapters support ICH Q3D, offering additional guidance on measurement procedures that can be employed to evaluate the presence and concentrations of metal impurities. Since 2018, all pharmaceutical companies supplying to the U.S. market must comply with USP and . Advanced XRF equipment is capable of meeting all these standards.

Further Reading

For more information on XRF and how it can help in determining the purity of pharmaceuticals, check out the following great resources.

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