A primary goal of analytical chemistry is to provide robust, sensitive, selective, and efficient tools and techniques for the analysis and understanding of vast range of analytes. For analytes relevant to both human health and the environment, a critical need is to analyze an increasingly large number of compounds with decreasing detection limits, including ultra-trace (parts-per-trillion and lower) concentrations of analytes. Additionally, a major consideration for all analytical techniques is the number of complex and varied matrices in which analytes must be measured. For these samples there is a strong need to develop sample preparation techniques that increase analyte recovery and allow for improved instrumental analysis. Developments and applications of analytical chemistry are then driven by the advances in and needs of other scientific fields, including those in environmental and human health applications.My thesis work focuses on the development of preparation and instrumental analysis methods for analytes relevant to the human health and the environment across a variety of sample types and matrices. Of particular interest is the application of liquid chromatography, tandem mass-spectrometry (LC-MS/MS) measurements for highly selective and sensitive analysis of two classes of analytes, each its own project. The first project involves per- and polyfluoroalkyl substances (PFAS), a class of more than 12,000 compounds which are defined by a characteristic perfluorinated carbon moiety which confers water- and oil-repellent properties. This class of compounds has found widespread use in both industrial and commercial applications since the 1950s, though, research increasingly shows hazards posed to both humans and the environment from these persistent compounds. My thesis work seeks to identify new or poorly described applications of PFAS in consumer goods and to define the concentrations and types of PFAS used through a combination of analytical techniques. My developed analytical methods, described in Chapter 3, are applied to the measurement of PFAS in various consumer goods as described in Chapter 2 with a focus on cosmetics, and Chapters 4 and 5 with focus on plastic products.In Chapter 2, the occurrences of PFAS in North American cosmetics is shown through the measurement of elevated total fluorine concentrations in more than 50% of 231 cosmetic products analyzed. Targeted analysis results for select PFAS in 29 cosmetic products showed that all products contained detectable amounts of PFAS, at parts-per-billion and higher concentrations. Results from this work also highlight the lack of disclosure or labeling of PFAS presence in these cosmetic products and describes the regulatory landscape of cosmetic labeling in the United States and Canada. In Chapter 4, the use of fluorinated polymer processing aids in the manufacturing of thin-film and molded plastics is examined through the measurement of 39 plastic products. Results from this work illustrate the presence of both polymeric and non-polymeric forms of PFAS present in the plastic samples through total fluorine and targeted analysis measurements. In Chapter 5, the occurrences of perfluorocarboxylic acids (PFCAs) in directly fluorinated containers is explored. This work examines the amounts of PFCAs present in directly fluorinated plastics and focuses on the rates and routes of migration of these PFCAs into the goods that are stored in directly fluorinated containers. Parts-per-billion concentrations of PFCAs were shown to migrate into water, methanol, acetone, various foods, and into two indoor household products in as little as one week, demonstrating significant direct and indirect routes of exposure from directly fluorinated plastics.The second project centers on illicit substances found in street drug samples and is concentrated on those that contribute to both nonfatal and fatal overdoses in the ongoing opioid and synthetic opioid epidemic. This work seeks to demonstrate the applicability of LC-MS/MS analysis and workflows as a useful tool for independent, community and academic-based drug checking and harm reduction services to offer information on drug composition and concentrations in illicit street drug samples. Chapters 6 and 7 focus on the development of two targeted analysis methods for the analysis of illicit drugs. The first of these methods, described in Chapter 6, includes analysis of a total of 22 illicit drugs including opioids and stimulants. Results from the analysis of 124 street drug samples collected in Chicago, IL showed high occurrences of opioids, namely the synthetic opioid fentanyl, across samples. In Chapter 7, the same samples collected from Chicago, IL were screened against an LC-MS/MS method developed for 53 benzodiazepines. Results from this work highlight the occurrence of various benzodiazepines, especially designer benzodiazepines, in 86% of samples screened.