Ensuring the purity of pharmaceuticals and how XRF can fast-track elemental analysis
When you’re training to become a chemist or pharmaceutical scientist, you focus on learning how to form new chemical bonds. Much of your time is spent learning to perform reactions designed by chemists from times gone by. In industry, when you’re making real molecules for real patients, you spend just as much of your time (sometimes more!) on the purification of your molecules. That’s because creating the next best-in-class treatment requires the ability to produce the molecules in a pure form.
Nowhere is this more important than in the fields of scale-up and process development research for manufacturing.
Determining the purity of pharmaceutical drugs
When developing synthesis processes for pharmaceutical APIs, it is critical to ensure that elemental impurities associated with metal catalysts are scavenged prior to downstream processing.
Metal catalysts are a cornerstone of organic chemistry and play a vital role in a number of chemical transformations. However, when used in the synthesis of pharmaceutical APIs, it’s critical to ensure that elemental impurities associated with these catalysts are scavenged down to parts per million (ppm) levels prior to downstream processing.
The effectiveness of scavenging processes is typically determined using inductively coupled plasma spectroscopy (most commonly ICP-OES or ICP-MS). While ICP is highly accurate at detecting very low concentrations of elemental impurities, it’s a very time-consuming and expensive process; waiting for results delays process development decisions and can bring your project to a halt while you wait for results.
Overcoming the pain points of ICP
As the costs and risks associated with drug development continue to rise, pharmaceutical scientists must find innovative ways to improve efficiency across all phases of research and development. And you need to do it without compromising the quality and reliability of your analysis, or you’ll face regulatory compliance challenges as well!
Over the years, my colleagues and I have interviewed many pharmaceutical scientists who use ICP. Through these conversations, we have come across a number of pain points that these customers encounter with ICP.
PAIN POINTS OF ICP USERS
- Slow feedback loop due to the time needed for sample preparation
- It’s not possible to put ICP in remote places or at production lines – due to the infrastructure & utilities required
- It’s very labor intensive – ICP requires dedicated, highly trained operators
- ICP requires the use of hazardous chemicals, which are dangerous to users and bad for the environment
- It has a high cost of operation
- It’s difficult to measure halogens
- Accidents with the chemicals and glassware
- There are no screening tools
In this list of pain points, sample preparation is a BIG one that keeps coming up. It’s a very tedious and lengthy process because you have a powdered sample that needs to be dissolved in a liquid. This process can take anywhere from 24 to 48 hours, depending on the sample, elements and concentrations, and even longer if you have to outsource your analysis.
XRF: A robust solution for ensuring the purity of pharmaceuticals
X-ray fluorescence (XRF) is a rapid, easy-to-use, and easy-to-deploy tool for screening elemental impurities in support of drug synthesis process development. XRF can be used as a cost-effective and time-efficient means of performing metal catalyst scavenging to assist in the optimization of drug synthesis processes.
The safe manufacture and delivery of pharmaceutical products requires companies to ensure that patient exposure to toxic elements such as lead (Pb), mercury (Hg), arsenic (As) and cadmium (Cd) is controlled within safe limits as part of their drug dosage regimens. In response to this need, the International Conference on Harmonization (ICH) has issued guidance in ICH Q3D on acceptable exposure limits for 24 potentially toxic elements in oral, parenteral, and inhaled drug products. Compendial guidance, such as that provided in United States Pharmacopeia (USP) chapters <232> and <233>, supports ICH Q3D and provides additional guidance on the measurement procedures that can be used to assess the presence and concentration of elemental impurities. As of 2018, compliance with USP <232> and USP <233> is required for all pharmaceutical companies supplying the US market. High-end XRF instruments can meet all of these standards.
Further reading
To learn more about XRF and how it can help you determine the purity of pharmaceuticals, check out these great resources: