Anti-Doping Crisis in Sports, What's Next? Ion Mobility-Mass Spectrometry for the Study of Anabolic Androgenic Steroids
Date of Award
Doctor of Philosophy (PhD)
Biomedical and Chemical Engineering and Sciences
Christopher D. Chouinard
The main objective of this work is to augment both qualitative and quantitative measures of anabolic androgenic steroids (AAS) with ion mobility-mass spectrometry (IM-MS), laying the foundation for implementation into analytical drug testing laboratories. AAS testing requires high sensitivity and specificity. IM-MS is presented as an emerging technology workflow capable of targeted quantification of AAS and structural elucidation for potential unknowns, allowing ions to be separated and characterized based on their rotationally averaged collision cross section (CCS). Chapter 1 provides a background of the basic principles of IMS and the different types of analytical methods used for doping analysis currently and in the past. Chapter 2 demonstrates the characterization of nearly half the World Anti-Doping Agency (WADA) prohibited anabolic steroids, producing unique collision cross section (CCS) values, and in some instances, providing separation for isobars and isomers. Chapter 3 presents increased resolution with structurally selective reagent 1,1-carbonyldiimidazole (CDI), targeting hydroxyl groups. Girard’s Reagent P derivatization is used for carbonyl derivatization, allowing increased ionization efficiency due to its fixed charge quaternary amine. Parallel reactions are additionally studied for improved IM resolution, sensitivity, and structural characterization. Chapter 4 further explores derivatization reagents for improving AAS mobility resolution. Alcohol group derivatizing reagents included PTSI, dansyl chloride, and FMPTS, while carbonyl derivatization reagents were MOA and HP. Bile acids derivatization with CDI is processed with high-resolution demultiplexer (HRdm) to demonstrate increased resolution without altering instrumentation conditions. The final chapter presents a quick summary and further research needed. Suggestions on covalent shift reagents based on literature research for both individual and parallel reactions are given, in addition to recommendations for analysis in neat mixtures and complex biological matrices. Potential for structural elucidation and isomer resolution based on unique fragmentation diagrams from data-dependent MS/MS analysis is discussed in addition to suggested optimized reaction automation.
Velosa, Diana Constanza, "Anti-Doping Crisis in Sports, What's Next? Ion Mobility-Mass Spectrometry for the Study of Anabolic Androgenic Steroids" (2023). Theses and Dissertations. 1245.
Available for download on Monday, May 06, 2024
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