Along with a series of studies we plan to present related to our experiences with hybrid LC-MS/MS technology, KCAS will also be presenting on a study where we analyzed a compound that involved looking at urea in plasma and lung fluid (urea, of course, being a biomarker).
Urea is endogenous in the body, so it has its own inherent set of challenges from that perspective – rather than simply being just being drug you might administer. Also, just because of the nature of polar molecules, it makes analysis by LC-MS more difficult. Because it is a polar molecule, every step of the way we were utilizing extraction chromatography and mass spectrometry, and each step had its own set of challenges, requiring recalibration and focus on optimization.
Historically, the methods that would be used in a study like this would suggest using GC-MS with derivatization or isotope dilution methods. So utilizing a LC-MS assay was a fresh approach, but for the extraction, we couldn’t simply go with a typical protein precipitation model. We had difficulty with retention, then in the mass spectrometer, too, because of the low molecular weight – creating challenges with background interference from matrix components. So we had to look into two different matrices – plasma and bronchial alveolar lavage. Then, with it being endogenous, we had to look for surrogate matrix that would work when measuring in both matrices.
What made KCAS the ideal place to conduct these studies?
KCAS has a good method development team who is experienced in method development. In this case, we were able to develop the assay by just pulling on our years of experience within Brian’s team to develop the necessary assay that addresses all these unique challenges. Our MS teams have a lot of experience with biomarkers from these very low molecular weights, all the way through to much bigger proteins – and beyond.
Who will be most interested in this presentation in Barcelona?
EBF is an ideal meeting for these case studies, as it is the key bioanalysis meeting in Europe. Large Pharma and Small Pharma organizations from across Europe (and, indeed, the world) will be there, and virtually all of them would benefit from hearing about the experiences we’ve had with these case studies. The stories about what we’ve done with biomarkers across the board will be of value to all of them.
So if you’re in Barcelona for EBF this year, this is a presentation you will not want to miss!
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