Conjugation with the tripeptide glutathione (GSH) is a common mechanism of detoxification of many endogenous and exogenous compounds. This phenomenon typically occurs through the formation of a covalent bond between the nucleophilic free thiol moiety of GSH and an electrophilic site on the compound of interest. While GSH adducts have been identified for many licit drugs, there is a lack of information on the ability of drugs of abuse to adduct GSH. The present study utilized a metabolic assay with GSH as a nucleophilic trapping agent to bind reactive drug metabolites formed in situ. Extracted ion MS spectra were collected via LC-QqQ-MS/MS for all potentially significant ions and examined for fragmentation common to GSH-containing compounds, followed by confirmation of adduction and structural characterization performed by LC-QTOF-MS/MS. In addition to the two positive controls, of the 14 drugs of abuse tested, 10 exhibited GSH adduction, with several forming multiple adducts, resulting in a total of 22 individual identified adducts. A number of these are previously unreported in the literature, including those for diazepam, naltrexone, oxycodone and Δ-THC.

All rights reserved by the author with the exception of Figures 6 and 7. Figures 6 and 7 have been included with the permission of the respective publishers. iv DEDICATION This is dedicated to my friends and family who have helped me not only through my time in graduate school but also through life. I should hope to someday be able to impart the wisdom, strength, forgiveness, love, and generosity which you have all shown to me. "I do not feel obliged to believe that the same God who has endowed us with senses, reason, and intellect has intended us to forego their use…"-Galileo Galilei v ACKNOWLEDGMENTS I would like to first acknowledge my advisor, Dr. Anthony DeCaprio. You have been able to challenge me to achieve so much in my time at FIU, and you have been there to provide support, feedback, and ideas when I was in need of any of the three. I would like to thank my committee members, Dr. Bruce