A method was developed for preconcentration, separation, and determination of arsenic species [As(III), As(V), DMA, and MMA] in water samples by flow injection solid phase extraction hydride generation atomic absorption spectrometry. Competing anion interferences were minimized by employing two anion-exchange columns in series. The method was successfully applied for the determination of trace concentrations in various water samples spiked with a mixture of arsenic species. A new method was developed for the determination of ultra-trace amounts of As(III) and As(V) by flow injection solid phase extraction hydride generation atomic absorption spectrometry with tetrahydroborate immobilized on an anion-exchange substrate. The method offers several advantages including simplicity, sensitivity improvement, arsenic speciation, cost reduction and less waste generation compared to the conventional hydride generation AAS method. The method was successfully applied to the determination of As(III) and As(V) in different kinds of environmental water samples including well water, lake water, tap water, spring water, and sea water. A new method was developed for the determination of As(III), As(V), DMA and MMA by high performance liquid chromatography hydride generation inductively coupled plasma optical emission spectrometry. The new multimode sample introduction system (MSIS) was employed instead of a conventional gas-liquid separator. The separation was achieved with good resolution and detection limits by using an anion-exchange column, either an IonPac AS10 or an Alltech Anion HC column. The extraction of arsenic species from soils was significantly improved with a sequential extraction procedure. Arsenic species extracted were successfully separated and determined by high performance liquid chromatography hydride generation inductively coupled plasma optical emission spectrometry with the MSIS. No significant changes in the arsenic species were observed during the extraction. A method was developed for improving the detection of the Hach test kits. Solid phase extraction was used for the preconcentration of arsenic in water samples prior to testing by the Hach kit. The color intensity for all concentrations including those close to 10 μg l-1 was increased. The method was successfully applied to environmental water samples spiked with low arsenic concentrations.

The instrumental limit of detection (LOD) lies at the heart of modern analytical chemistry, yet there is still much debate as to its role and reliability as a figure of merit. There are a number of possible ways to define the LOD, and in the present work four such sample test statistics were defined and their probability density functions (PDFs) were derived. The PDFs were easily evaluated via numerical integration and were used to obtain expectation values, population precisions, and confidence intervals. Monte Carlo simulation methods were used to prepare normalized histograms of one million LOD variates each, for homoscedastic linear calibration curve systems, and these were found to be in excellent agreement with the numerically obtained PDFs and associated statistics. With the realization that LODs are random variates governed by their PDFs it becomes evident that the quotient of two LODs is also a random variate governed by its own distribution. One case of a limit of detection definition was taken and the theoretical PDF for the quotient of two LODs was derived. Monte Carlo simulations were again used to generate normalized histograms of one million quotient of LOD variates, and were also in excellent agreement with the numerically evaluated theoretical PDF. In addition to the simulation and theoretical approaches, a real chemical measurement system was designed in an effort to collect large data sets that could be used to obtain experimental LODs. The data collected on the measurement system was carefully analyzed and, after a randomization algorithm, was deemed appropriate to generate a normalized histograms of quotients of LOD (in some cases up to 40,000 points). It was found that the distribution of values obtained from the real system almost perfectly matched that of the derived theory and Monte Carlo simulation providing a sound argument for the conclusions we have drawn. The software used in all aspects of the work is available with full commented source code.

Methods for the determination of trace elements in environmental and biological samples were developed and optimized. Parameters affecting sample introduction efficiency, matrix effects, sample throughput and tolerance to interfering species were evaluated for methods based on plasma spectrochemistry and electrochemistry. A method was developed for the determination of copper in the presence of β-2-microglobulin. A mass balance of copper was performed at the end of in vitro incubations which required method development to quantify copper in the liquid and solid portions of the incubation solutions, along with copper adsorbed and mass transferred into the walls of the incubation vessel. A flow injection method was developed to accommodate the small sample volume and high dissolved solids content to allow for the determination of copper by ICP-MS. A commercial introduction system was evaluated for the determination of trace elements in drinking waters and wastewaters by ICP-MS and ICP-OES. Parameters including increased throughput, reduced memory effects, increased stability and lower reagent consumption were evaluated as the system was successfully applied to U.S. EPA Methods 200.8 and 200.7, respectively. Particular attention was paid to the retention of mercury and sodium and long term stability during the analysis of samples containing high total dissolved salts. Results obtained with the new introduction system were compliant with EPA Methods 200.8 and 200.7 while increasing sample throughput two- or three-fold and significantly reducing memory effects. A method was developed for the enhancement of signals for trace elemental analysis by DRC-ICP-MS. Signal enhancement was evaluated as instrumental and reaction gas parameters were optimized. Background noise levels remained relatively unchanged as signal intensities were improved, resulting in improved signal to noise ratios. The developed method was successfully applied to the determination of gold in synthetic geological samples. A method was developed for the preconcentration and speciation of arsenic by anodic stripping voltammetry using ion exchange resins. Ion exchange and instrument parameters were optimized. The developed method was successfully applied to the determination of arsenic(III) and arsenic(V) in waters without interference from problematic species such as Cu(II). Suitable detection limits were obtained and the method was validated using a certified reference material.

Methods for the simultaneous determination and speciation of arsenic, selenium and antimony in complex matrices involving inductively coupled plasma optical emission spectrometry (ICP-OES), and inductively coupled plasma mass spectrometry (ICP-MS) coupled with high performance liquid chromatography (HPLC) were developed and successfully applied to the analyses of various types of environmental and biological samples. A flexible internal standardization procedure for ICP-OES has been developed that extends the choices of possible internal standards and has the potential for greater accuracy than traditional internal standardization based on one standard. This method is based upon the visualization by principal component analysis of the similarity of matrix-induced behavior among emission lines. For a given analytical line, more choices of internal standards are provided from composite spectral lines created by combining real spectral lines in such a way as to integrate their characteristic behaviors. The method was applied with satisfactory results to the determination of As, Sb and Se in solutions which modeled plant and food sample digests to compensate for the matrix effect. A method for the simultaneous determination of As, Sb and Se by the multimode sample introduction system coupled to ICP-OES has been developed. Reaction mechanisms for sample treatment and hydride generation are proposed to account for some unusual observations. In order to study urinary arsenic and selenium metabolism and interactions in the human body, a procedure for the simultaneous determination of six Se species and six As species in human urine by HPLC-ICP-MS has been developed. Positive associations between As intake and urinary Se metabolites, Se intake and urinary As metabolites were found. As and Se interactions may increase the mobility of both species in human tissue or blood, and as a result, more As and Se may be excreted. The competition for methyl groups between As and Se species changes the distribution of As and Se metabolites in human urine. The excretion of methylated species are delayed. The formation of monomethylated species is enhanced while that of multimethylated species is inhibited when both As and Se are ingested.

The precursor of open chain Reissert analogues was prepared by reaction of mandelonitrile with aniline to form 2-anilino-2-phenylacetonitrile. A range of open chain Reissert compounds was made by reacting the acetonitrile with p-nitrobenzoyl chloride, p-methylbenzoyl chloride, and p-methoxybenzoyl chloride. Each of the Reissert compounds was treated with fluoroboric acid to form the munchnone iminium salt. Each was reacted with ethyl propiolate and ethyl phenylpropiolate to yeild highly substituted pyrroles. The ratio of the regioisomeric products of each of the reactions was established by HPLC. Identification of the regioisomers was accomplished by alternate syntheses, and by 300 MHz ('1)H-NMR analyses. Based on the regiochemical data gathered, 1,3 dipolar cycloaddition reactions of munchnone iminium salts with substituted acetylenes are highly regioselective. Regioisomeric product ratios indicate that merostabilization has a greater effect on the regiochemistry of the reaction than Linnett stabilization, which in turn is stronger than benzylic stabilization for the reactions of munchnone iminium salts with substituted acetylenes.

Mass spectrometry-based proteomics has become an important and versatile tool in analytical chemistry, making sense of complex biological samples and shedding light on the intricate proteomes of living organisms. Bottom-up proteomics studies are used to elucidate the changes in gene expression of bacteriophage T7 over the course of infection of Escherichia coli. E. coli cultures were infected with T7, sampled over time, and proteins were isolated and enzymatically digested. Nanoflow liquid chromatography combined with tandem mass spectrometry was used to detect proteolytic peptides and identify host and phage proteins. Generally, phage proteins were detected on a time scale fitting the established lytic cycle for T7 phage, confirming the effectiveness of infection monitoring by mass spectrometry-based proteomics studies. Continued development of the experimental method sought to increase detection of proteolytic peptides and identify phage and host proteins to a higher level of confidence, and lead to the implementation of 1D SDS-PAGE as a fractionation method to reduce sample complexity and increase method sensitivity.

The goal of this dissertation is to develop applications for metal selective gas chromatographic detection by microwave-induced plasma atomic emission spectroscopy. A new commercial GC-AED system is used in the examination and analysis of a wide variety of metal-containing compounds. The performance of the GC-AED for selective detection of model compounds containing aluminum, gallium, chromium, vanadium, cobalt, nickel, palladium and copper is evaluated. Figures-of-merit are reported for these compounds. For aluminum, gallium, chromium, vanadium and palladium, new recipes are developed for the AED concerning digital filters for continuous background correction and experimental parameters such as emission wavelength, helium flow rate and reagent gases, as well as discharge tube materials. The separations of the diastereoisomers of VO(pnTFA$\sb2$) are demonstrated by both capillary GC and HPLC. GC-AED proved valuable in the study of gas phase diastereoisomerism of the tetradentate oxovanadium Schiff base chelates. Picogram detection limits for vanadium by GC-AED facilitated study of kinetic behavior at low concentrations. Multielement detection for metal and nonmetals in the chelates provided identification of eluted peaks. HPLC coupled with DCP and PDA detection assisted the study of the isomerization in solutions. Methods are developed for the characterization of chromium $\beta$-diketone polymers by GC-AED and GC-MS following pyrolysis. Thermal stability is reported for a series of chromium and cobalt chelates and their polymers. Element specific detection proved to be superior in screening metal-containing pyrolysates and simplifying the interpretation of other fragments. High temperature GC-AED is developed for the analysis of vanadyl, nickel and iron porphyrins in crude oils. Limits of detection, precision and inter-element selectivity between vanadium, nickel and iron are reported. The metal elution profiles are characteristic for different oils and compatible for fingerprinting the oils from different fields. The method is also advantageous in the study of decomposition of petroleum metal species. Quantification of the metal profiles indicates the contents of the distillable metals to be generally lower than those of total metals determined by the direct spectroscopic methods. A study on the distribution of metalloporphyrins in crude oils is also carried out by gel permeation chromatography. A correlation between total metal, metalloporphyrin and total distillable metal contents is addressed in this study. Sample pretreatment procedures to remove heavy oil matrices prior to the GC-AED analysis are investigated. Solvent extraction in combination with solid phase extraction is used to extract volatile metal species favorably. GPC proved to be even more effective and reproducible in the resolution of volatile metal species into clean and defined fractions.

Capillary column GC-MIP was applied to trifluorinated gallium, indium, and copper $\beta$-diketonates, a tetradentate copper $\beta$-ketoaminate, ferroceneboronate derivatives of diols and cyclopentadienyl rhodium dicarbonyl. The chemically inert fused-silica capillary column showed improved GC characteristics for the metal chelates. Excellent GC characteristics of the organometallic compounds were observed. The MIP parameters for Ga, In, Cu, Rh, Fe and B elements were investigated and optimized. Detection limits and selectivities against carbon for these elements were determined. Gas chromatography with sensitive and element selective MIP detection was employed to study ligand exchange reactions between fluorinated gallium, indium, aluminum, copper and nickel $\beta$-diketonates which occurred in chloroform. The ligand exchange reactions between gallium chelates showed statistical redistribution of ligands. HPLC study of ligand exchange reactions between fluorinated gallium, indium, copper and nickel $\beta$-diketonates proved that these reactions could occur in liquid phase. The process of ligand exchange reaction between two fluorinated gallium $\beta$-diketonates (Ga(TFA)$\sb3$ and Ga(TTB)$\sb3$) was monitored and the kinetic parameters such as reaction rate constant and overall reaction order of this reaction were determined with HPLC. MIP detection proved valuable for GC analysis of diols through their ferroceneboronate derivatives. The response factors for both iron and boron specific detection were consistent for both pinacol and dicyclohexyl-1,1$\sp\prime$-diol ferroceneboronates. Pyrolysis-GC of tetradentate salicyladimine ligand and copper and nickel chelates was carried out to study the thermal fragmentation patterns of these materials. Mass spectrometric detection, as well as parallel FID and NPD detection, was employed. The use of a capillary column improved the peak shapes and resolution of the fragment compounds. The two major fragment compounds were phenol and o-methyl phenol. The central metal appeared to have little influence on the patterns of major fragment peaks.

Electrochemical and ultraviolet detection are two detection techniques used most often in flow injection analysis (FIA) and high performance liquid chromatography (HPLC). When these detectors are operated below a signal-to-noise ratio (S/N) of three, the precision of replicate determinations exceeds ten percent relative standard deviation (RSD). This dissertation demonstrates how cross correlation was used to improve the S/N in real-time at a fixed time delay (zero seconds) in both FIA and HPLC. A flow injection (FI) response below a S/N of three is cross correlated with another FI response of very high S/N. In one case, both FI responses are generated simultaneously by operating the FI systems in parallel and then cross correlating their outputs using an analog correlation circuit. In another case, a computer is used to digitize and store a high S/N FI response. After each injection, the high S/N FI signal is cross correlated with the injection response using the analog correlation circuit. The dynamic range of the amperometric detector was extended an order of magnitude after cross correlation. The lowest standard of dopamine determined after correlation was 0.12nM. The S/N at this level was 130, an improvement of 28 over the direct detector response. The detection limit at S/N = 3 was 3 $\times$ 10$\sp{-12}$M dopamine, corresponding to 63fg injected. When blank solutions were injected into a flowing stream injection peaks were observed. A novel injection technique is implemented in this work, which positions a valve downstream from the sample plug and separates the sample response from the injection peak. The use of this injection technique with cross correlation allowed detection of dopamine at the 0.84nM level at a S/N = 92, which corresponds to a detection limit for dopamine of 0.03nM. The increase in detection limit using this technique is due to increased dispersion in the flow system and increased pump noise due to the use of peristaltic pumps. Cross correlation has also been used to improve the S/N in the HPLC separation of catecholamines. Cross correlation resulted in an improvement in S/N 20 times better than that obtained using low pass filtering.

Different methods of sample introduction for inductively coupled plasma mass spectrometry (ICP-MS) when a limited volume of a sample is available were investigated in this research. The methods include pneumatic nebulization, recirculating nebulization (RN) systems (internal pneumatic nebulization), flow injection (FI), and ultrasonic nebulization (USN). All these sample introduction methods for ICP-MS were tested for their usefulness for quantitative and semi-quantitative analyses and isotopic ratio measurements. Samples as small as 0.250 mL can be analyzed for a few minutes, and 1 mL of a sample can be analyzed for over 60 minutes when RN-ICP-MS is employed. This time allows either a semi-quantitative analysis or isotopic ratio measurements to be performed. Flow injection was found to be a reliable method for quantitative analysis performed in a sample-to-standard addition mode. Testing of a prototype of an ultrasonic nebulization system demonstrated the potential of this technique, as a result of its superior sensitivity compared to pneumatic nebulization. However, some modifications of the design are necessary to improve the USN performance as a method of sample introduction for ICP-MS.