Of all the chemical processes in the fine chemical and pharmaceutical industries, cross-coupling reactions are among the most important. This often involves platinum group metal (PGM) catalysts, which then must be separated from the product to avoid contamination of the product by these regulated elemental impurities (USP<232>), as well as avoiding that these valuable materials enter the waste stream.
Here is where the process chemists step in to save the day, developing methods to scavenge metal catalyst, tailored for effectiveness with each new compound. This is an iterative process, and metals analysis after each step is key to this development process. Enter the new best friend to process chemists in the pharmaceutical industry – the Epsilon 1 benchtop X-ray Fluorescence (XRF) system. The Epsilon 1 is the ideal analytical solution for quantification of ruthenium, rhodium, palladium, iridium, and platinum in pharmaceutical materials, compliant ready for 21CFR part 11.
I spoke with a research scientist in a metals lab at a major pharmaceutical innovator and learned how the Epsilon 1 has enhanced the speed of process development.
“We use the Epsilon 1 primarily for analysis of metal catalyst scavenging. Compounds can come from research with relatively high levels of metal catalyst such as Palladium (Pd), and our process chemists develop ways to decrease these metals. The Epsilon 1 provides (near) instant feedback for next steps decisions by process chemists,” explains the research scientist.
At this site, about a dozen process chemists have been trained to operate the Epsilon 1, and a system has been placed in their lab, as well as in the metals lab. “We can easily develop new methods on our system in the metals lab and deploy them to the system in the process lab” stated the scientist.
In their metals lab, the queue for an ICP metals analysis can be several weeks long. There is also a concern for ICP system contamination when high levels (>1000ppms) of a metal catalyst such as Pd are run through the system. It takes a lot of effort to clean the system so that a subsequent low-level Pd containing sample can be accurately measured. So offloading what amounts to hundreds of analyses per month to the Epsilon 1 has had a big impact.
How can the Epsilon 1 save a pharmaceutical company money?
Speed of development – having the Epsilon 1 in the process lab can shave months off the scavenger method development process, because there is no downtime waiting for ICP analysis – “results take as little as 2 minutes”.
Sample recovery – because the Epsilon 1 is non-destructive, the sample can be put back into the process stream. “This is huge – development is often limited to sample sizes of a gram or less, so the ability to recover, reuse, or send the sample on for another test is key.”
Sample preparation time savings – “it might require a dissolution study in order to find the right solvent for an ICP analysis of a new compound”, but XRF samples are measured as is, whether in powder or liquid form. In addition to time savings, a potential source of error – dilution – is removed.
Chemical waste reduction – samples are measured as is, and either returned to the process stream or sent on to another analytical technique – so there is no chemical waste produced by using the Epsilon 1.
Flexibility – although pre-calibrated to analyze five key metals used as catalysts, it is straightforward to add additional element calibrations to the method. “Now when the process chemists measure their samples, they might care about a particular catalyst element, but they are getting accurate results simultaneously on a dozen elements for which we have calibrated the system. We have also developed methods for counter ion analysis on the Epsilon 1.”
The researcher added, “when new process chemists join, it generally takes 30 minutes to train them to use the Epsilon 1, then once they complete an additional radiation safety course they are able to use the system in their lab.” “So, you are teaching people to fish?” I asked. “Yes, you can say that!”