Extractables&Leachables Small Molecule Impurity ID - Current Approaches and Opportunities
Analytical scientists across industries are often tasked with identification of small molecule impurities in extractables and leachables (E&L) studies of materials used in biomedical devices, contacts and closures (C&C), labels and packaging. Impurity ID is also a key activity throughout the drug development process. Successful identification of an impurity facilitates its thorough toxicological risk assessment, and helps R&D teams make important chemicals and materials sourcing and processing decisions.
Liquid and gas chromatography coupled to various detection platforms are both heavily utilized for low concentration impurity analysis. Mass spectrometry detectors have over the last decade improved in resolution, mass accuracy, as well as dynamic range. Consistent instrumentation and software improvements now also allow very high sensitivity detection and quantitation of impurities.
High resolution mass spectrometry systems can be used to identify the accurate mass, and often the elemental composition of an impurity. Elemental composition alone, however, does not guarantee structural identification, in fact, most often a combination of analytical techniques is required. Orthogonal chromatography retention and UV data, coupled with high resolution MS fragmentation of a known impurity mass, helps to narrow down the number of possible structures that can explain a given intact accurate mass and its fragments.
This series of the Mass Spec Lab blogs is dedicated to those analytical scientists, R&D managers, and teams who have a high vested interest in successful impurity ID. In this series, we will showcase, in a case study format, E&L impurity identification of rubber additives. We will share data from aforementioned techniques, but also move beyond the typical high resolution MS hardware and data acquisition software capabilities into the territory of chemical computation. We plan to show how we use MassFrontier1,2 (Thermo, HighChem) theoretical fragment prediction software, and discuss the need for computational structure generators, such as MOLGEN3.
We invite you to take a look at the recently presented case study poster 'Determination of an Unknown E&L Impurity Based on Accurate Mass Detection, Elemental Composition Matching, Chemicals Database Searching, and MassFrontier Theoretical Fragmentation'
We want to hear from you . Please tell us about your experience and approaches in successful small molecule impurity ID. What instrumentation do you currently use, is it LC-UV, low or high resolution GC-MS or LC-MS? Have you considered or are you currently using computational structure and fragment prediction to help with structural elucidation of impurities? Please do share the successes, but also the caveats, the difficulties that often arise due to chromatography, ionization efficiency, and ambiguity of elemental composition and MS fragmentation. When we share both the successes and difficulties, as we intend to do in this blog, we collectively learn the most. Look forward to your feedback! Mass Spec Lab team.
1 V. Petrusevski, S.T. Jolevska, J.T. Ribarska, M. Chachorovska, A. Petkovska, S. Ugarkovic (2016) Development of complementary HPLC-DAD/APCI MS methods for chemical characterization of pharmaceutical packaging materials, Journal of Pharmaceutical and Biomedical Analysis, Vol 124, p.228
2 Hua Yang, Kate Comstock, Linda Lopez (2014) Comparison of Soxhlet and Accelerated Solvent Extraction for Leachable and Extractable Analysis of Packaging Material, ThermoScientific Application Note 1108
3 Ralf Gugisch, Adalbert Kerber, Axel Kohnert, Reinhard Laue, Markus Meringer, Christoph Rücker, Alfred Wassermann (2014) MOLGEN 5.0, a Molecular Structure Generator In: Advances in Mathematical Chemistry and Applications, Vol. 1 Edited by:Subhash C. Basak, Guillermo Restrepo, José L. Villaveces. 113-138 Bentham Science Publishers Ltd.