Document Type

Thesis - Open Access

Award Date


Degree Name

Doctor of Philosophy (PhD)

Department / School

Chemistry and Biochemistry

First Advisor

Brian A. Logue


Evolutionary algorithms, Isotope ratio mass spectrometry, Isotope ratios, Liquid chromatography, Nonlinear molecular modeling, Nonlinear numerical solvers


Isotope ratios (IRs) are a measure of the variation in abundance of light isotopes versus heavy isotopes of an element, e.g. 1H/2H,12C/13C, and 14N/15N. Because IRs change as a molecule undergoes certain chemical and physical processes, they represent unique fingerprints that can be used to trace the source of a chemical compound. Current techniques for determination of IRs each have major limitations, such as loss of structural information, vulnerability to contamination, high cost, large sample size requirements, low precision, limited applicability, and lengthy analysis. Fast Isotope Ratio Mass Spectrometry (FIRMS) was developed as a next-generation analytical technique for robust measurement of IRs using tandem mass spectrometric data. Based on the FIRMS nonlinear mathematical model, the difference between predicted and experimental tandem mass spectrometric data was minimized by modifying isotopic fractional abundances of the atoms involved. FIRMS was used to calculate the isotope abundances of molecules of 17 compounds. FIRMS produced excellent precision, with IRs standard deviations of less than 1‰, for δ13C compared with IRMS in a fraction of the time. FIRMS also produced excellent accuracy for δ13C values with an absolute error of less than 1.6‰ compared to IRMS. It was also successfully coupled with LCMSMS to analyze δ13C for DIMPA, caffeine and acetylsalicylic acid with standard deviation of less than 1‰ and accuracies within 1‰ compared to IRMS. The bivariate plot of FIRMS versus IRMS showed an excellent R2 of 0.992 with a slope of 1, validating the new technique as an accurate isotope ratio measurement technique. FIRMS offers several advantages over other methods of IR determination, and may ultimately become the preferred method for determination of IRs. The disciplines that will benefit from development of FIRMS include: 1) forensic science, 2) environmental chemistry, 3) geology, 4) geochemistry, 5) cosmochemistry, 6) food sciences, 7) earth science, and 8) pharmaceutical science. FIRMS will make IR analysis more widely available, fast and less expensive for scientists to conduct research in these fields, as well as train new graduate students for future scientific research and development in this area.

Library of Congress Subject Headings

Mass spectrometry.
Tandem mass spectrometry.


Includes bibliographical references (pages 114-126)



Number of Pages



South Dakota State University



Rights Statement

In Copyright