Graduation Semester and Year
Spring 2026
Language
English
Document Type
Thesis
Degree Name
Master of Science in Chemistry
Department
Chemistry and Biochemistry
First Advisor
Kevin Schug
Second Advisor
Saiful Chowdhury
Third Advisor
Daniel Armstrong
Abstract
Small aldehydes such as formaldehyde and acetaldehyde are highly reactive metabolites that play important roles in biological processes related to oxidative stress, metabolism, and DNA damage. Because of their chemical reactivity, volatility, and low endogenous concentrations, accurate measurement of these compounds in biological samples remains analytically challenging. The goal was to develop and evaluate a practical analytical method for detecting small aldehydes in biologically relevant matrices using headspace gas chromatography mass spectrometry (HS-GC-MS). The method combined chemical derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and headspace sampling to stabilize aldehydes and enable selective detection by mass spectrometry. Method development focused on optimizing derivatization conditions, chromatographic separation, headspace sampling parameters, and detection settings to achieve reproducible aldehyde detection. Under optimized conditions, aldehyde derivatives were separated using an HP-5MS capillary column and detected using selected ion monitoring (SIM). Validation experiments performed using aqueous calibration standards demonstrated reproducible analyte detection with strong calibration linearity and low variability across replicate analyses. Following aqueous validation, the method was applied to practice plasma matrices to evaluate matrix dependent behavior. Plasma analysis revealed several important challenges, including substantial endogenous formaldehyde background and matrix dependent variability in analyte detectability and internal standard performance across different plasma additives. These results demonstrated that practical quantification limits in plasma were higher than those observed in aqueous systems due to endogenous background contributions and matrix related signal suppression. This work demonstrates that HS-GC-MS combined with aldehyde derivatization provides a useful framework for detecting reactive aldehydes in biological samples. At the same time, the results highlight the importance of evaluating matrix effects when translating methods from controlled systems to complex biological matrices. The approach developed provides a foundation for future work investigating aldehyde metabolism, oxidative stress, and reactive carbonyl chemistry in biological systems.
Keywords
Aldehydes, Plasma, PFBHA, Derivatization, Quantification
Disciplines
Analytical Chemistry | Forensic Chemistry
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Clark, Stephanie T., "Development and Validation of an Analytical Method for Quantitative Determination of Small Aldehydes in Plasma" (2026). Chemistry & Biochemistry Theses-Archive. 122.
https://mavmatrix.uta.edu/chemistry_theses/122
Comments
I would like to first thank my advisor, Dr. Kevin Schug, for his guidance, support, and patience throughout this project. I am grateful for the opportunity to work in his laboratory and for the experience and perspective I gained during my time in the group. His mentorship helped shape both this research and my development as a scientist.
I would also like to thank my committee members, Dr. Saiful Chowdhury and Dr. Daniel Armstrong, for taking the time to serve on my committee and for providing thoughtful feedback that helped improve this work.
I am very grateful to the members of the Schug laboratory, both past and present, for their support, advice, and the many helpful discussions that took place along the way. Research is rarely a straight path, and having people around who are willing to share ideas, troubleshoot problems, and celebrate small successes makes a big difference.