Novel solid-phase extraction techniques for biological and environmental analysis using isotope dilution mass spectrometry.

摘要

Awareness and study of the ways in which the environment can interact with the personal genetics and epigenetics of an individual has grown substantially in recent years, resulting in the field of Exposomics. In an era of increasingly personalized medicine, novel techniques are necessary to ensure the accurate and sensitivity measurement of clinically and environmentally relevant molecules in biological and environmental samples. Addressing existing shortcomings cited in literature, methods were developed and optimized for the extraction, separation, mass analysis, and quantification of a suite of environmental organic pollutants in both biological and environmental samples, with the primary objective of improving accuracy, increasing sensitivity, and reducing sample and reagent consumption. The secondary objective of this research was the production of validated methods capable of inter-laboratory method transfer with minimal training required in the receiving laboratory. Two novel methods have been developed, optimized, validated, and applied to collaborative environmental research. These novel methods represented a demonstrative improvement upon existing methods in both analytical quality and capability for inter-laboratory method transfer. Both developed methods were utilized in two collaborative clinical research studies investigating the impact of environmentally-sources agents on children diagnosed with autism spectrum disorders (ASD). The high-quality data obtained in these studies yielded results that may have provided valuable insight into the development and maintenance of autism spectrum disorders. These novel methods allowed for the discovery of a first-of-its-kind variable in the children with ASD, compared with controls. This variable was statistically predictive for the probability of an individual being diagnosed with the most behaviorally severe autism disorder, with a statistically significant overall model fit. This novel analytical method was then expanded in breadth through application to industrial and municipal wastewater to aid in updating EPA Method 625 for wastewater analysis. Applying this novel method to wastewater produced data of higher analytical quality, in both accuracy and precision, compared with all other collaborative laboratories. The methods developed in this work for the quantification of organic molecules implicated in environmental human health in biological and environmental samples have significantly improved analytically upon existing methods and have yielded clinically relevant findings in collaborative clinical research studies.