In pharmaceutical analysis, precision, accuracy, and efficiency are paramount. There is a constant need for methodologies that streamline analytical processes while maintaining the integrity of results. Amidst this pursuit, solid phase microextraction (SPME) emerges as a promising technique poised to play a key role in certain aspects of pharmaceutical analysis.
SPME is a sample preparation technique that involves extracting and concentrating analytes from a sample onto a coated fiber, which acts as a sorbent. Key steps include exposing the fiber to the sample, allowing the analytes to partition between the sample and the fiber coating, and desorbing the analytes for analysis.
Unlike traditional extraction techniques that often involve cumbersome processes and solvent consumption, SPME offers a simple, solvent-free approach for extracting and concentrating analytes from complex matrices.
SPME's versatility extends across a range of applications, including environmental monitoring and food analysis. However, compared to other industries, its adoption in pharmaceutical analysis has been relatively limited, and static headspace analysis continues to dominate.
Advantages of SPME Over Other Methods
A key advantage of SPME is its low detection limit. Gyorgy Vas, owner of Vas Analytical, describes the tribromoanisole (TBA) impurity issue that impacted Johnson and Johnson in 2010: "This was a huge quality issue coming from wood pallets. Even large companies were forced to use plastic pallets for pharma packaging." One of the validated methods for detecting TBA at parts per trillion levels was SPME. According to Vas, no other technique was able to achieve such a level. "SPME can achieve single-digit ppb or even below ppb for certain analytes in a matter of minutes. A traditional approach might take days to reach the same answer."
Aside from low detection limits, SPME offers another significant advantage in the form of automation. "It's very easy to automate," says Vas, explaining that today's robotic autosamplers make SPME methods a breeze. "You just place the solid tablet in the headspace vial spiked with the internal standard, and boom—the robot does the job."
One more attractive feature of SPME is that it's a solventless technique, which offers obvious sustainability benefits as well as cost savings. "Solvent use is labor-intensive," explains Vas. "It requires additional work to perform the solvent-based extraction, plus you have to dispose of the solvents." There are health considerations involved with solvents, too. "In certain states, you need special permission to use solvents such as diethyl ether due to health concerns," warns Vas. "There are no such requirements for SPME."
SPME is admittedly not a one-size-fits-all method and has its limitations. "If your target analytes have a low logP, for example, below 3.5, and you have an aqueous matrix, SPME is usually not your tool," says Vas. "But if the size of the target is in the optimal range, SPME can be a great technique."
Slow Adoption Within Pharma
Vas continues to explain that SPME is unlikely to be broadly adopted in pharmaceutical analysis. "At levels between 0.5 and 5 ppm, there is method overlap—while SPME would work, other methods are suitable." However, he notes that some specific use cases could definitely benefit from SPME. One of those is toxic impurities such as polynuclear aromatics. "SPME is very good for this application," advises Vas. "Even directly from solid matrices, it's excellent for screening presence or absence. There are limitations with exact quantitation, but it is ideal for determining if the concerning analyte is present in your matrix."
A barrier to using SPME within pharma is one that we often hear within the industry. As is the case with many other potentially useful technologies, adoption is slow because the method is not widely recognized by regulators. Vas notes that one ISO standard does indicate the use of SPME for aqueous extracts. But for the most part, it remains an unknown technique that people are unwilling to adopt. "While the R&D side of pharma is highly innovative, testing methods are very conservative and everything needs to be so QC friendly," says Vas. "Analysts stick to using static headspace, which is great in some respects but can be unsuitable for many applications."
Considerations When Designing a SPME Method
If a pharmaceutical analyst does decide to use a SPME method, there are some key considerations, but Vas stresses that no specialized knowledge is required. "You follow the same criteria as you would with a classical static headspace method," he explains. "You are optimizing the equilibrium temperature, equilibrium time, fiber chemistry, and extraction time. And that's it."
One aspect that requires caution is consistency between batches of SPME fiber. Reproducibility is extremely important within pharma, so Vas recommends using the same quality, and ideally batch, of fiber each time. "We performed a study that showed variation between the extraction performance of various batches. Even with the variation, you can still see the target peaks, but the intensities were very different."
While traditional methods continue to dominate within pharmaceutical analysis, the inherent advantages of SPME beckon exploration. Advantages such as enhancing efficiency, reducing solvent consumption, and facilitating automation hold significant promise in various fields.
This article is featured in our May 2024 publication, Pharmaceutical Purity and Precision. Find out what’s happening in the world of pharmaceutical impurity analysis and learn about the latest topics and techniques.
