But, when it comes to detecting lies with technology we must measure multiple parameters: blood pressure, skin conductivity, pulse and respiration to even have a chance of detecting a fib. No single physical parameter is an ultimate source of truth – but by combining several factors you can build a strong case.
The same goes for analyzing unknown contaminants in pharmaceuticals, such as extractable and leachable impurities. The workhorse system for identifying unknowns is typically mass spectrometry as discussed in my previous blog . However, with LC-MS, the ability to identify a compound is directly related to how effectively it can be ionized. If it doesn’t ionize you can’t detect it.
No single ionization mode covers all analytes. Usually impurity or stability studies are conducted with a variety of ionization modes. Typically APCI & ESI are employed in the effort to ensure that unknown compounds do not go undetected. Even then, many compounds do not ionize. Moreover, ionization efficiencies in mass spectrometry are so widely varied that quantitation is only credible when accompanied with a variety of suitable internal and external standards.
For pharmaceutical impurities it is fundamental to know both compound identity and amount of all impurities, so that a confident risk assessment can be conducted.
So, how do you detect and quantify the un-ionizable?
Well most LC-MS systems employ some form of orthogonal detection device; most commonly UV based detectors. But UV detectors also suffer from analogous challenges to MS. Firstly, that analytes must have a chromophore; secondly, UV detection sensitivity shows marked differences in detector response, even for isomers. So what’s the answer?
Charged aerosol detection (CAD) is a well-established, near universal LC detection technology that provides a consistent response that is independent of the analyte’s chemical structure. This is especially useful for detecting substances without chromophores and the quantification of unknowns without a comparable chemical standard. The technology is now available as a detection module for the Thermo Scientific™ Vanquish™ UHPLC system and is a perfect complement to the identification capabilities of mass spectrometry.