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The field of electrospray ionization mass spectrometry is reviewed with emphasis placed upon advances in the elucidation of fundamental mechanistic aspects of the ionization process that have been reported over the past 10 years. The analytical consequences of these findings are also examined. Eight central conclusions or 'tenets' are presented, as deduced from the body of work contained in 80 references.where r c is the capillary outer radius, V c is the applied electric potential and d is the distance from the capillary tip to the counter-electrode. The electric field strength is typically ¾10 6 -10 7 V m 1 . 2,3 As ionic species in the sample solution emerge from the ESI capillary, they undergo electrophoretic movement in response to the imposed electric field. In the positive ion mode, anions

High-resolution mass spectrometry (HRMS) has become a vital tool for dissolved organic matter (DOM) characterization. The upward trend in HRMS analysis of DOM presents challenges in data comparison and interpretation among laboratories operating instruments with differing performance and user operating conditions. It is therefore essential that the community establishes metric ranges and compositional trends for data comparison with reference samples so that data can be robustly compared among research groups. To this end, four identically prepared DOM samples were each measured by 16 laboratories, using 17 commercially purchased instruments, using positive-ion and negative-ion mode electrospray ionization (ESI) HRMS analyses. The instruments identified~1000 common ions in both negative-and positive-ion modes over a wide range of m/z values and chemical space, as determined by van Krevelen diagrams. Calculated metrics of abundance-weighted average indices (H/C, O/C, aromaticity, and m/z) of the commonly detected ions showed that hydrogen saturation and aromaticity were consistent for each reference sample across the instruments, while average mass and oxygenation were more affected by differences in instrument type and settings. In this paper we present 32 metric values for future benchmarking. The metric values were obtained for the four different parameters from four samples in two ionization modes and can be used in future work to evaluate the performance of HRMS instruments.

Nonadherence to antihypertensive treatment is a critical contributor to suboptimal blood pressure control. There are limited and heterogeneous data on the risk factors for nonadherence because few studies used objective-direct diagnostic methods. We used high-performance liquid chromatography-tandem mass spectrometry of urine and serum to detect nonadherence and explored its association with the main demographic- and therapy-related factors in 1348 patients with hypertension from 2 European countries. The rates of nonadherence to antihypertensive treatment were 41.6% and 31.5% in the UK and Czech populations, respectively. Nonadherence was inversely related to age and male sex. Each increase in the number of antihypertensive medications led to 85% and 77% increase in nonadherence (<0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications (≤0.005 in both populations). The predictive model for nonadherence, including age, sex, diuretics, and the number of prescribed antihypertensives, showed area under the curves of 0.758 and 0.710 in the UK and Czech populations, respectively. The area under the curves for the UK model tested on the Czech data and for the Czech model tested on UK data were calculated at 0.708 and 0.756, respectively. We demonstrate that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure-lowering therapy. Further development of discriminatory models incorporating these parameters might prove clinically useful in assessment of nonadherence in countries where biochemical analysis is unavailable.

Background: Combustion generated particulate matter is deposited in the respiratory tract and pose a hazard to the lungs through their potential to cause oxidative stress and inflammation. We have previously shown that combustion of fuels and chlorinated hydrocarbons produce semiquinone-type radicals that are stabilized on particle surfaces (i.e. environmentally persistent free radicals; EPFRs). Because the composition and properties of actual combustion-generated particles are complex, heterogeneous in origin, and vary from day-to-day, we have chosen to use surrogate particle systems. In particular, we have chosen to use the radical of 2-monochlorophenol (MCP230) as the EPFR because we have previously shown that it forms a EPFR on Cu(II)O surfaces and catalyzes formation of PCDD/F. To understand the physicochemical properties responsible for the adverse pulmonary effects of combustion by-products, we have exposed human bronchial epithelial cells (BEAS-2B) to MCP230 or the CuO/silica substrate. Our general hypothesis was that the EPFR-containing particle would have greater toxicity than the substrate species.

Attachment of small anions to neutral molecules is an important ionization mechanism in negative ion electrospray mass spectrometry. In this report, the tendency for different anions to remain attached to selected analyte compound classes has been systematically investigated. A rationale for the formation and stability of preferred anionic adducts is proposed in light of thermodynamic considerations. A series of collision-induced dissociation experiments reveals that the gas-phase basicities of the deprotonated analyte molecule ([M - H]-) and the anion moiety play important roles in determining the stability of anionic adducts. Adducts of the form [M - H]-...H+...[anion]- manifest increased stability when the two anions have similar gas-phase basicities. Within certain limitations, the difference in deltaG degrees values for proton combination with [M - H]- and with [anion]- can be used as a first-order predictor of adduct stability. In addition, stability increases with the rising gas-phase basicities of the two moieties. The specific interaction between a small inorganic anion (bisulfate) and a neutral analyte molecule (alpha-D-glucose) in the form of multiple hydrogen bonding has also been affirmed by computer modeling to contribute to the stability of some anionic adducts. Last, the gas-phase basicity of deprotonated alpha-D-glucose (i.e., the gas-phase acidity of alpha-D-glucose) is determined by a "bracketing method" to be in the range of 1373-1407 kJ/mol.

The field of electrospray ionization mass spectrometry is reviewed with emphasis placed upon advances in the elucidation of fundamental mechanistic aspects of the ionization process that have been reported over the past 10 years. The analytical consequences of these findings are also examined. Eight central conclusions or 'tenets' are presented, as deduced from the body of work contained in 80 references.

A newly invented probe accessory for fast electrochemistry/electrospray mass spectrometry (EC/ESMS) is presented and evaluated. The device features a low-volume, three-electrode electrochemical cell which has been designed with a minimum distance between the working electrode and the "Taylor cone" inherent to the electrospray process. This configuration limits the time between electrochemical generation of ions and mass spectrometric analysis to an absolute minimum. A fused-silica layer insulates the microcylinder working electrode from the sample solution until immediately prior to the electrospray region, postponing electrode processes until the last moment. The same fused-silica layer insulates the working electrode from the surrounding auxiliary electrode, a stainless steel capillary that also serves as the electrospray capillary. The performance and capabilities of the novel electrochemistry/electrospray mass spectrometry system have been evaluated using polycyclic aromatic hydrocarbons (PAHs) as test analytes. In the positive ion EC/ESMS mode, oxidized forms (one-electron removal) of PAHs are produced in high yield. The ability to analyze reaction products appearing subsequent to the initial oxidation is also demonstrated.