Atmospheric pressure chemical ionization of fluorinated phenols in atmospheric pressure chemical ionization mass spectrometry, tandem mass spectrometry, and ion mobility spectrometry

Atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) for fluorinated phenols (C6H5-xFxOH Where x = 0-5) in nitrogen with Cl- as the reagent ion yielded product ions of M Cl- through ion associations or (M-H)- through proton abstractions. Proton abstraction was controllable by potentials on the orifice and first lens, suggesting that some proton abstraction occurs through collision induced dissociation (CID) in the interface region. This was proven using CID of adduct ions (M Cl-) with Q2 studies where adduct ions were dissociated to Cl- or proton abstracted to (M-H)-. The extent of proton abstraction depended upon ion energy and structure in order of calculated acidities: pentafluorophenol > tetrafluorophenol > trifluorophenol > difluorophenol. Little or no proton abstraction occurred for fluorophenol, phenol, or benzyl alcohol analogs. Ion mobility spectrometry was used to determine if proton abstraction reactions passed through an adduct intermediate with thermalized ions and mobility spectra for all chemicals were obtained from 25 to 200 degrees C. Proton abstraction from M Cl- was not observed at any temperature for phenol, monofluorophenol, or difluorophenol. Mobility spectra for trifluorophenol revealed the kinetic transformations to (M-H)- either from M Cl- or from M2 Cl- directly. Proton abstraction was the predominant reaction for tetra- and penta-fluorophenols. Consequently, the evidence suggests that proton abstraction occurs from an adduct ion where the reaction barrier is reduced with increasing acidity of the O-H bond in C6H5-xFxOH.     

Atmospheric pressure matrix-assisted laser desorption/ionization with analysis by ion mobility time-of-flight mass spectrometry

The use of an atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) source was employed with an atmospheric pressure ion mobility spectrometer (APIMS) and an orthogonal acceleration reflector time-of-flight mass spectrometer (TOFMS) to analyze dipeptide and biogenic amine mixtures from a liquid glycerol 2,5-dihydroxybenzoic acid (DHB) matrix. Improved sensitivities were obtained by the addition of a localized electrical (corona) discharge in conjunction with the AP-MALDI source. Enhanced sample ionization efficiency created by this combination provided an overall elevation in signal intensity of approximately 1.3 orders in magnitude. Combinations of three dipeptides (Gly-Lys, Ala-Lys, and Val-Lys) and nine biogenic amines (dopamine, serotonin, B-phenylethylamine, tyramine, octopamine, histamine, tryptamine, spermidine, and spermine) were resolved in less than 18 ms. In many cases, reduced mobility constants (K(o)) were determined for these analytes for the first time. Ion mobility drift times, flight times, arbitrary signal intensities, and collision-induced dissociation (CID) fragmentation product signatures are reported for each of the samples.     

Study of atmospheric pressure chemical ionization of PETN by ion mobility spectrometry/tandem mass spectrometry

We present the results of studying the effects of temperature and humidity of the reaction medium and the intensity of ultraviolet radiation on the atmospheric pressure chemical ionization of Penthrite. The peculiarities of the ion mobility spectra of this compound obtained by ion mobility spectrometry-tandem mass spectrometry are analyzed.     

Atmospheric pressure ionization mass spectrometry

Atmospheric pressure ionization has been used to great effect by mass spectrometrists in widely diverse fields. The aim of this brief review is to set down the advantages of API/MS to fundamental and analytical chemists alike through discussion of the basic processes of ionisation and through its application.     

Low pressure chemical ionization in ion trap mass spectrometry

This article presents the specificities of low pressure chemical ionization in ion trap mass spectrometry. One main feature is the ability to perform chemical ionization with liquid reagents as readily as with "conventional" gases (methane, isobutane and ammonia). The reactivities and analytical applications of gas and liquid reagents are summarized from literature data and are compared when possible.     

Atmospheric-pressure ionization studies and field dependence of ion mobilities of isomeric hydrocarbons using a miniature differential mobility spectrometer

The ionization pathways and ion mobility were determined for sets of structural isomeric and stereoisomeric non-polar hydrocarbons (saturated and unsaturated cyclic hydrocarbons and aromatic hydrocarbons) using a novel miniature differential mobility spectrometer with atmospheric-pressure photoionization (APPI) to assess how structural and stereochemical differences influence ion formation and ion mobility. The analytical results obtained using the differential mobility spectrometry (DMS) were compared with the reduced mobility values measured using conventional time-of-flight ion mobility spectrometry (IMS) with the same ionization technique.The majority of differences in DMS ion mobility spectra observed among isomeric cyclic hydrocarbons can be explained by the formation of different product ions. Comparable differences in ion formation were also observed using conventional IMS and by investigations using the coupling of ion mobility spectrometry with mass spectrometry (APPI-IMS-MS) and APPI-MS. Using DMS, isomeric aromatic hydrocarbons can in the majority of cases be distinguished by the different behavior of product ions in the strong asymmetric radio frequency (rf) electric field of the drift channel. The different peak position of product ions depending on the electric field amplitude permits the differentiation between most of the investigated isomeric aromatics with a different constitution; this stands in contrast to conventional IMS in which comparable reduced mobility values were detected for the isomeric aromatic compounds.     

Atmospheric pressure chemical ionization mass spectrometry of aldehydes in biological matrices

Application of high-performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) for detection of aldehydes in biological samples such as blood, yoghurt, and milk, is reported. Sample preparation is easy, and the presented method is both sensitive and selective. It is based on the widely used dinitrophenylhydrazine derivatization, followed by extraction with n-hexane and a simple reversed-phase HPLC separation. Detection is performed by atmospheric pressure chemical ionization (APCI) in negative ion mode, with detection limits in the low picogram range. Using MS/MS, acetone and propionaldehyde can clearly be distinguished, facilitating propionaldehyde quantitation even in the presence of high acetone levels. Quantitation by direct MS/MS is also feasible, well suited for high-throughput applications, although not as accurate as using HPLC/MS/MS.     

Atmospheric pressure chemical ionization mass spectrometry and in-source fragmentation of lutein esters

Negative-ion atmospheric pressure chemical ionization (APCI) mass spectrometry and in-source collisionally induced dissociation (CID) were employed to obtain structural information of lutein esters from marigold extract. Both molecular ions and structurally significant fragments corresponding to the loss of fatty acids were observed in high abundance in the current study. Six lutein diesters including lauroylmyristoyl-lutein (LML), dimyristoyl-lutein (dML), myristoylpalmitoyl-lutein (MPL), dipalmitoyl-lutein (dPL), palmitoylstearoyl-lutein (PSL) and distearoyl-lutein (dSL) were characterized in a marigold flower extract. Breakdown curves (plots of relative ion abundance vs. internal energy) of three lutein diesters were established by monitoring the relative ion abundance of molecular and fragment ions at different cone voltages during negative-ion APCI-LC/MS analysis.     

Subambient pressure electrospray ionization ion mobility spectrometry

The pressure dependence of sheath gas assisted electrospray ionization (ESI) was investigated based on two complementary experimental setups, namely an ESI-ion mobility (IM) spectrometer and an ESI capillary - Faraday plate setup housed in an optically accessible vacuum chamber. The ESI-IM spectrometer is capable of working in the pressure range between 300 and 1000 mbar. Another aim was the assessment of the analytical capabilities of a subambient pressure ESI-IM spectrometer. The pressure dependence of ESI was characterized by imaging the electrospray and recording current-voltage (I-U) curves. Qualitatively different behavior was observed in both setups. While the current rises continuously with the voltage in the capillary-plate setup, a sharp increase of the current was measured in the IM spectrometer above a pressure-dependent threshold voltage. The different character can be attributed to the detection of different species in both experiments. In the capillary-plate experiment, a multitude of charged species are detected while only desolvated ions attribute to the IM spectrometer signal. This finding demonstrates the utility of IM spectrometry for the characterization of ESI, since in contrast to the capillary-plate setup, the release of ions from the electrospray droplets can be observed. The I-U curves change significantly with pressure. An important result is the reduction of the maximum current with decreasing pressure. The connected loss of ionization efficiency can be compensated by a more efficient transfer of ions in the IM spectrometer at increased E/N. Thus, similar limits of detection could be obtained at 500 mbar and 1 bar.     

Two-dimensional separations with electrospray ionization ambient pressure high-resolution ion mobility spectrometry/quadrupole mass spectrometry

The coupling of ion mobility spectrometry (IMS) instruments with mass spectrometers has been described since early in IMS development, most commonly with quadrupole mass analyzers. The recent development of IMS with time-of-flight (TOF) instruments has demonstrated that the time compatibility (IMS milliseconds and TOFMS microseconds) of the two techniques enables rapid two-dimensional separations to be performed, theoretically in the order of seconds for a complete analysis. This study presents a unique way to operate a traditional IMS/QMS system to attain separations similar to those achieved with IMS/TOF. For this new approach, the quadrupole was slowly scanned in the single-ion monitoring mode while IMS spectra were continually embedded in each m/z step. In this way, two-dimensional separations (IMS drift times and m/z) were obtained using the traditional IMS/QMS arrangement. An example of a five amino acid separation (quadrupole scan of 40 m/z values at a rate of approximately 7 steps/min) led to a complete two-dimensional analysis within 6 min, comparable to rapid chromatographic separations with mass spectrometry. Proposed approaches to reduce the analysis time are discussed and a reduction in the analysis time to less than 1 min is feasible when the IMS/QMS separation conditions are optimized.     

Negative ion atmospheric pressure ionization mass spectrometry: Ionization of aromatic hydrocarbons

A corona discharge atmospheric pressure ionization source generates the reagent ions, OH^? and O^? ions in addition to better known O₂^? ions, when ambient air is used as the carrier. All three ions are gas-phase bases that could form negative ions from organics via proton abstraction. Ionization of simple aromatic hydrocarbons by O₂^? is thermodynamically not feasible. Simple aromatic hydrocarbons are ionized only by O^? and/or OH^? to form [M ? H]^? ions. However, [M ? H]^? ions do not appear in the mass spectrum as they undergo stabilization via clustering with predominantly oxygen atoms.     

Desorption electrospray ionization mass spectrometric analysis of organophosphorus chemical warfare agents using ion mobility and tandem mass spectrometry

Desorption electrospray ionization mass spectrometry (DESI‐MS) has been applied to the direct analysis of sample media for target chemicals, including chemical warfare agents (CWA), without the need for additional sample handling. During the present study, solid‐phase microextraction (SPME) fibers were used to sample the headspace above five organophosphorus CWA, O‐isopropyl methylphosphonofluoridate (sarin, GB), O‐pinacolyl methylphosphonofluoridate (soman, GD), O‐ethyl N,N‐dimethyl phosphoramidocyanidate (tabun, GA), O‐cyclohexyl methylphosphonofluoridate (cyclohexyl sarin, GF) and O‐ethyl S‐2‐diisopropylaminoethyl methyl phosphonothiolate (VX) spiked into glass headspace sampling vials. Following sampling, the SPME fibers were introduced directly into a modified ESI source, enabling rapid and safe DESI of the toxic compounds. A SYNAPT HDMS? instrument was used to acquire time‐aligned parallel (TAP) fragmentation data, which provided both ion mobility and MSⁿ (n = 2 or 3) data useful for the confirmation of CWA. Unique ion mobility profiles were acquired for each compound and characteristic product ions of the ion mobility separated ions were produced in the Triwave? transfer collision region. Up to six full scanning MSⁿ spectra, containing the [M + H]⁺ ion and up to seven diagnostic product ions, were acquired for each CWA during SPME fiber analysis. A rapid screening approach, based on the developed methodology, was applied to several typical forensic media, including Dacron sampling swabs spiked with 5 µg of CWA. Background interference was minimal and the spiked CWA were readily identified within one minute on the basis of the acquired ion mobility and mass spectrometric data. Copyright © 2010 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.     

Evaluation of micro-electrospray ionization with ion mobility spectrometry/mass spectrometry

In recent years, the resolving power of ion mobility instruments has been increased significantly, enabling ion mobility spectrometry (IMS) to be utilized as an analytical separation technique for complex mixtures. In theory, decreasing the drift tube temperature results in increased resolution due to decreased ion diffusion. However, the heat requirements for complete ion desolvation with electrospray ionization (ESI) have limited the reduction of temperatures in atmospheric pressure ion mobility instruments. Micro-electrospray conditions were investigated in this study to enable more efficient droplet formation and ionization with the objective of reducing drift tube temperatures and increasing IMS resolution. For small molecules (peptides), the drift tube temperature was reduced to ambient temperature with good resolution by employing reduced capillary diameters and flow rates. By employing micro-spray conditions, experimental resolution values approaching theoretically predicted resolution were achieved over a wide temperature range (30 to 250 °C). The historical heat requirements of atmospheric pressure IMS due to ESI desolvation were eliminated due to the use of micro-spray conditions and the high-resolution IMS spectra of GLY-HIS-LYS was obtained at ambient temperature. The desolvation of proteins (cytochrome c) was found to achieve optimal resolution at temperatures greater than 125 °C. This is significantly improved from earlier IMS studies that required drift tube temperatures of 250°C for protein desolvation.     

Traveling-wave ion mobility mass spectrometry analysis of isomeric modified peptides arising from chemical cross-linking

Traveling-wave ion mobility (TWIM) coupled to mass spectrometry (MS) has emerged as a powerful tool for structural and conformational analysis of proteins and peptides, allowing the analysis of isomeric peptides (or proteins) with the same sequence but modified at different residues. This work demonstrates the use of the novel TWIM-MS technique to separate isomeric peptide ions derived from chemical cross-linking experiments, which enables the acquisition of distinct product ion spectra for each isomer, clearly indicating modification on different sites. Experiments were performed with four synthetic peptides, for which variable degrees of mobility separation were achieved. In cases of partially overlapping mobility arrival time distributions (ATDs), extracting the ATDs of fragment ions belonging to each individual isomer allowed their separation into two distinct ATDs. Accumulation over regions from the specific ATDs generates the product ion spectrum of each isomer, or a spectrum highly enriched in their fragments. The population of both modified peptide isomers was correlated with the intrinsic reactivities of different Lys residues from reactions conducted at different pH conditions.     

Atmospheric pressure ionization permanent magnet fourier transform ion cyclotron resonance mass spectrometry

A new Fourier transform ion cyclotron resonance mass spectrometer based on a permanent magnet with an atmospheric pressure ionization source was designed and constructed. A mass resolving power (full-width-at-half-maximum) of up to 80,000 in the electron ionization mode and 25,000 in the electrospray mode was obtained. Also, a mass measurement accuracy at low-ppm level has been demonstrated for peptide mixtures in a mass range of up to 1200 m/z in the isotopically resolved mass spectra.     

Tetraalkylammonium halides as chemical standards for positive electrospray ionization with ion mobility spectrometry/mass spectrometry

Chemical standards for positive ion mode electrospray ionization ion mobility spectrometry/mass spectrometry (ESI(+)-IMS/MS) are suggested. The low clustering tendency of tetraalkylammonium halides makes them ideal chemical standards for ESI(+)-IMS/MS. A homologous series of these compounds forms a useful external standard for instrument testing and resolution calibration of an IMS instrument. Selected homologues or a mixture of tetraalkylammonium halides can be used as mobility standards in the analytical runs. Absolute and relative reduced mobilities were calculated for C2--C8, C10 and C12 tetraalkylammonium halides. Absolute reduced mobilities in nitrogen were 1.88, 1.56, 1.33, 1.15, 1.02, 0.92, 0.84, 0.73, and 0.67 cm2 V(-1) s(-1), for C2--C8, C10 and C12 tetraalkylammonium halides, respectively. Relative reduced mobilities (relative to 2,6-di-tert-butylpyridine) for the same compounds were 1.20, 1.00, 0.855, 0.743, 0.658, 0.59, 0.54, 0.47, and 0.43, respectively.