= Emerging. More than 5 years before clinical availability. (24.37%, 2023)
= Expected to be clinically available in 1 to 4 years. (39.50%, 2023)
= Clinically available now. (36.13%, 2023)
MSACL 2023 : Strathmann

MSACL 2023 Abstract

Self-Classified Topic Area(s): Emerging Technologies > Assays Leveraging MS > Tox / TDM / Endocrine

Podium Presentation in Steinbeck 1 on Thursday at 10:20 (Chair: Robin Kemperman / Carrie Adler)

PFAS Dark Matter and Slippery Cannabis: Disparate Problems with a Similar Path to a Solution

Frederick G. Strathmann, Rachel A. Harris, Joshua K. McBee, Thomas Lubinsky, Julie Wuchensky, Heidi Vitrac
MOBILion Systems, Inc., Chadds Ford, PA 19317

Frederick Strathmann, PhD, MBA (Presenter)
MOBILion Systems

Presenter Bio: Fred has been in laboratory medicine for over 10 years and has held various positions including Assistant Professor of Pathology & Laboratory Medicine, Medical Director of Toxicology, Scientific Director of Mass Spectrometry, and Senior Vice President of Operations and R&D. He has worked in hospital and national reference laboratory environments, is board certified by the American Board of Clinical Chemistry in both Clinical Chemistry and Toxicological Chemistry and qualifies as a CLIA Certified Laboratory Director for High Complexity Testing. He completed his MS and PhD in Pathology & Laboratory Medicine and a postdoctoral fellowship in Biomedical Genetics from the University of Rochester School of Medicine and Dentistry in Rochester, New York, a Clinical Fellowship at the University of Washington in Seattle, Washington, and an MBA from the University of Utah in Salt Lake City, Utah. Fred is driven by the impact that laboratory testing has on healthcare outcomes and is thrilled to be a part of MOBILion’s mission and to help extend its capabilities into clinical diagnostics.

Abstract

INTRODUCTION:
PFAS compounds have a long and diverse history of applications yet only recently has sufficient attention been focused on the environmental and toxicological impacts of their use. The number of PFAS compounds has expanded rapidly and it is estimated that 5,000 to 10,000 PFAS compounds exist. Despite the tremendous numbers of PFAS compounds in existence, a relatively small number have been studied in depth and are commercially tested routinely. The term “PFAS Dark Matter” has emerged to signify the recognized gap between Total Organic Fluorine, Total Oxidizable Precursors, and targeted methods using tandem mass spectrometry for PFAS concentration assessment. It is estimated that nearly every individual has at least one PFAS present in their blood, and the toxicological significance of PFAS and the implications of the PFAS Dark Matter are far from being fully appreciated. Similarly multifarious, cannabis has a complex chemical composition that includes terpenes, sugars, hydrocarbons, steroids, flavonoids, amino acids, and other compounds of potential interest. More than 700 natural constituents have been identified and more than 100 are classified as cannabinoids. The toxicological community has been challenged with the appearance of isomers of various cannabinoids causing numerous analytical challenges with limited solutions beyond chromatographic run time extension. Though diverse in the context of the challenges presented, trends in PFAS and cannabinoid production and laboratory-associated detection methods are quickly evolving in a manner reminiscent of Novel Psychoactive Substances with similar complexities involving identification, testing, and interpretation of toxicological data.

OBJECTIVES:
The primary objective of this study was to leverage a relatively novel analytical combination of LC, HRIM and QTOF approaches to unravel the complexity seen with existing separation challenges. A secondary objective of this study was to call attention to the need for clinical laboratories to evolve beyond existing workflows in anticipation of the challenges with emerging analytical needs associated with higher complexity biomarkers on the horizon.

METHODS:
We used the MOBILion HRIM system based on Structures for Lossless Ion Manipulation (SLIM) to assess cannabinoids and PFAS in a variety of matrices. A combination of Flow Injection Analysis or Liquid Chromatography with HRIM was used prior to detection using an Agilent QTOF. Accurate mass, isotope spacing, isotope ratios, and mobility aligned fragmentation were used in various combinations for tentative and absolute identification depending upon available standards. In several cases, CCS values were derived providing a unique, molecular identifier that was leveraged to generate 2 dimensional plots of CCS vs. m/z to elucidate trendlines and characteristic subclasses revealing distinctive relationships within and across compound classes. Lastly, previously established CCS values were used to generate reference plots of CCS vs. m/z as a tool to understand potential impact of interferences with known, endogenous compounds where applicable.

RESULTS:
Herein we report our use of the MOBIE® high-resolution ion mobility system (HRIM) from MOBILion with an Agilent LC-QTOF system to resolve fourteen different cannabinoid species reported in cannabis including positional isomers delta-8 and delta-9 THC, with an approximately 0.4% CCS difference, sufficiently resolved in matrix-free samples in the absence of chromatographic separation. Eight previously identified perfluorooctane sulfonates including the tentative identification of one additional branched form previously unseen, were found with enhancement of existing chromatographic separation by the HRIM system. Lastly, we explored an emerging link between hemp and PFAS in a subset of available extracts as a potential consequence of phytoremediation efforts with implications into as yet unknown toxicological significance.

CONCLUSION:
The LC-HRIM-QTOF system used is a powerful combination that can be implemented to enhance existing LC workflows for deeper sample characterization, reduce LC reliance to boost throughput, and add CCS values to existing compound identification and classification approaches. The examples provided here are relatively simple analytical challenges where existing separation technology has been limited in its utility for long-term, routine use. The clinical laboratory field has been eagerly watching the various “omics” fields with the anticipation of multiomics, diagnostic test availability, yet we have been largely idle in integrating truly novel analytical techniques outside of molecular testing. As the intricacies of each of the omics fields continues to be unraveled, novel technologies being applied to applications residing on the outskirts of existing and established workflows hold promise for meeting the ever-increasing complexity of novel testing expectations to come.


Financial Disclosure

DescriptionY/NSource
Grantsno
SalaryyesMOBILion Systems
Board Memberno
Stockno
Expensesno
IP Royaltyno

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes