Mass spectrometry--not just a structural tool: the use of guided ion beam tandem mass spectrometry to determine thermochemistry

Guided ion beam tandem mass spectrometry has proved to be a robust tool for the measurement of thermodynamic information. Over the past twenty years, we have elucidated a number of factors necessary to make such thermochemistry accurate. Careful attention must be paid to the reduction of the raw data, ion intensities versus laboratory ion energies, to a more useful form, reaction cross sections versus relative kinetic energy. Analysis of the kinetic energy dependence of cross sections for endothermic reactions can then reveal thermodynamic data for both bimolecular and collision-induced dissociation (CID) processes. Such analyses need to include consideration of the explicit kinetic and internal energy distributions of the reactants, the effects of multiple collisions, the identity of the collision partner in CID processes, the kinetics of the reaction being studied, and competition between parallel reactions. This work provides examples illustrating the need to consider this multitude of effects along with details of the procedures developed in our group for handling each of them.     

A new tandem mass spectrometer for the study of molecular dissociations

A new tandem mass spectrometer has been developed for the study of molecular fragmentation reactions. The first stage of this tandem mass spectrometer is a double-focusing sector field instrument in the BE configuration. The second stage is a double-focusing combination of a Wien filter and a sector magnet that allows simultaneous detection of a wide range of masses owing to the approximately equal velocities of the fragment ions. By using a microchannel plate as a collision target, high fragmentation effi.ciency and high ion transmission were achieved.     

A collinear tandem time-of-flight mass spectrometer for infrared photodissociation spectroscopy of mass-selected ions

An apparatus based on collinear tandem time-of-flight mass spectrometer has been designed for the measurement of infrared photodissociation spectroscopy of mass-selected ions in the gas phase.The ions from a pulsed laser vaporization supersonic ion source are skimmed and mass separated by a Wiley-McLaren time-of-flight mass spectrometer.The ion of interest is mass selected,decelerated and dissociated by a tunable IR laser.The fragment and parent ions are reaccelerated and mass analyzed by the second time-of-flight mass spectrometer.A simple new assembly integrated with mass gate,deceleration and reacceleration ion optics was designed,which allows us to measure the infrared spectra of mass selected ions with high sensitivity and easy timing synchronization.     

Characterisation of new pyridazinofurocoumarins by electron ionisation and multiple stage tandem mass spectrometry using an ion trap mass spectrometer

The inverse electron-demand Diels-Alder reaction between furocoumarinones and 3,6-bis(methoxycarbonyl)-1,2,4,5-tetrazine was used to give pyridazinofurocoumarins in good yields. The structural characterisation of the synthesised compounds was achieved by NMR spectroscopy. The mass spectrometric behaviour was studied under electron ionisation conditions via sequential product ion fragmentation experiments (MS(n)). This study allowed the evaluation of the role played by the methyl substituent on the benzene ring of pyridazinofurocoumarins in their fragmentation pathways.     

Coupling a particle beam interface directly to a quadrupole ion trap mass spectrometer

A particle beam interface has been coupled to a quadrupole ion trap mass spectrometer. The system allows the collection of electron ionization mass spectra from analyte in solution. The interface incorporates a pneumatic nebulizer, a heated desolvation chamber, and a three-stage separator region. Additional helium, for improved performance, is added through stage 3. The particles formed in the interface are separated from solvent molecules and are transferred directly to the ion trap where they are expected to collide with the hot hyperbolic surface of the end cap. The end cap serves both as a heated target used to vaporize the particles and as an ion-trapping electrode. Mass analysis is achieved with the mass-selective instability scan supplemented with resonance ejection. Electron ionization spectra from 100 ng of caffeine [molecular weight (MW) = 1941; 1-naphthalenol methylcarbamate (carbaryl) (MW = 2011, 17α-hydroxyprogesterone (MW = 330), and reserpine (MW = 608) are shown using sampling by a segmented flow analysis. Some charge exchange is evident with methanol as well as self-chemical ionization at higher analyte levels. The interface shows a nonlinear caffeine calibration curve for analyte amounts below 30 ng and a more linear response at higher amounts. Caffeine was detected at 25 pmol (5 ng), with a signal-to-noise ratio of 50, 20-μL loop, full scan.     

Scanwave: A new approach to enhancing spectral data on a tandem quadrupole mass spectrometer

A new type of mass analyzer is described, which allows lowresolution axial ion ejection to be obtained from a traveling wave based, stacked ring collision cell. Linking this ejection temporally with the scanning of the second quadrupole of a tandem quadrupole mass spectrometer provides an improvement in sampling duty cycle, which results in significant signal intensity improvements for scanning acquisitions such as product ion spectra. A near 100% storage efficiency is enabled by a split cell design, which allows ion fragmentation and accumulation to be performed in one section of the collision cell whilst previously accumulated ions are simultaneously ejected from the rear of the cell. These characteristics combine to give an m/z-dependent signal gain of 7–20X over a conventional scanning quadrupole for a 1000 Th scan. The ability to swap very rapidly from a non-enhanced mode of operation to an enhanced mode whilst retaining the existing sensitivity, speed, and functionality of a conventional tandem quadrupole mass spectrometer is also described.     

Surface-induced dissociation of molecular ions in a quadrupole ion trap mass spectrometer

A method is reported by which surface-induced dissociation is used to activate ions stored in a quadrupole ion trap mass spectrometer. The method employs a short (< 5 μs), fast-rising (< 20-ns rise time), high voltage direct current (dc) pulse, which is applied to the endcaps of a standard Paul-type quadrupole ion trap. This is in contrast to the application of an alternating current (ac) signal normally used to resonantly excite and dissociate ions in the trap. The effect of the dc pulse is to cause the ions rapidly to become unstable in the radial direction and subsequently to collide with the ring electrode. Sufficient internal energy is acquired in this collision to cause high energy fragmentations of relatively intractable molecular ions such as pyrene and benzene. The dissociations of limonene are used to demonstrate that high energy demand processes increase in relative importance in the dc pulse experiment compared with the usual resonance excitation method used to cause activation. The fragments are scanned out of the ion trap using the conventional mass-selective instability scan mode. Simulations of ion motion in the trap provide evidence that surface collisions occur at kinetic energies in the range of tens to several hundred electronvolts. The experiments also demonstrate that production of fragment ions is sensitive to the phase of the main radiofrequency drive voltage at the point when the dc is initiated.     

A two-dimensional quadrupole ion trap mass spectrometer

The use of a linear or two-dimensional (2-D) quadrupole ion trap as a high performance mass spectrometer is demonstrated. Mass analysis is performed by ejecting ions out a slot in one of the rods using the mass selective instability mode of operation. Resonance ejection and excitation are utilized to enhance mass analysis and to allow isolation and activation of ions for MS(n) capability. Improved trapping efficiency and increased ion capacity are observed relative to a three-dimensional (3-D) ion trap with similar mass range. Mass resolution comparable to 3-D traps is readily achieved, including high resolution at slower scan rates, although adequate mechanical tolerance of the trap structure is a requirement. Additional advantages of 2-D over 3-D ion traps are also discussed and demonstrated.     

Mass-selected reagent ion chemical ionization and multiple tandem mass spectrometry techniques in an ion trap mass spectrometer for structural analysis

Mass-selected reagent ion chemical ionization (CI) performed in an ion trap instrument is an efficient tool to investigate gas-phase ion reactivities and therefore to find out new and/or optimized applications for structural analysis. For instance, it was shown that the C₃H₆O^{+ .} (58 mass units) molecular ion originated from vinyl methyl ether (VME) should necessarily be used alone (i.e. unit-mass selected) to produce significant diagnostic-ions for double bond location in aliphatic alkenes. Regarding the assignment of epoxides, the previous NO⁺/CI method was adapted for an optimal use in the trap through isolation of NO⁺ cation from N₂O (instead of NO) plasma and production of the acylium diagnostic-ions via CID of [M − H]⁺ formed by NO⁺-induced hydride abstraction. New alkylation ion-products, e.g. RCH = O⁺-al , were also found to characterize isomeric epoxides as a result of either an initial electrophilic addition of the C₂H₅⁺ cation (with saturated epoxides) or a methyl-transfer from [VME]^{+ .} (with α,β-unsaturated epoxides). The multiple tandem mass spectrometry (MSⁿ) capabilities of the ion trap were essential to achieve reagent ion mass-selection, structural assignment of the diagnostic-ions, or to provide further selectivity. © 1997 John Wiley & Sons, Ltd.     

An electrospray ionization source for thermochemical investigation with the guided ion beam mass spectrometer

An electrospray ionization (ESI) source developed for use with the guided ion beam tandem mass spectrometer (GIBMS) is described. For accurate determination of thermochemistry using threshold collision-induced dissociation (TCID), it is essential that any source produces ions with four exacting characteristics: (1) high intensity, (2) stable signal, and well-defined energies both (3) kinetic, and (4) internal. To accomplish these objectives, the ions generated by the electrospray are collected using a radio frequency electrodynamic ion funnel and are then transferred into a hexapole ion guide where they are thermalized and subsequently passed into higher-vacuum regions for analysis. The resulting ion intensities using this source can exceed 10(6) ions/s. Stable beams (<10% variation in signal) can be generated over multiple hours. The kinetic energy distribution of ions emerging from this source has been shown to be well described by a Gaussian distribution with a full width half maximum (FWHM) of about 0.1-0.2 eV in the laboratory frame of reference. Finally, TCID results for ions generated with this source show excellent agreement with previously reported threshold values for ions generated using a variety of sources and experimental methodologies. This confirms that internal energies of the ions are well described by a Maxwell-Boltzmann distribution at room temperature.     

A novel quadrupole,quistor, quadrupole tandem mass spectrometer

A quadrupole, quistor, quadrupole tandem mass spectrometer allowing selected ion/selected molecule reactions was built. The quistor will be used as a reaction chamber for the study of organic ion-molecule reactions. Ions are generated in a differentially pumped ion source, quadrupole mass selected and injected into the quistor. The ions are trapped in the quistor by the combined action of a deceleration lens, the presence of helium buffer gas and the quistor RF field. As a first test of the performance of the instrument, the reaction rate constant of the reaction of O₂⁺˙ with methane was measured to be 5 × 10^?12 cm³s^?1. This is in good agreement with literature values, indicating that the ions are near thermal equilibrium after a few milliseconds of trapping time.     

Conformer selection of protein ions by ion mobility in a triple quadrupole mass spectrometer

Electrospray mass spectra of multiply charged protein molecules show two distinct charge state distributions proposed to correspond to a more highly charged, open conformational form and a lower charged, folded form. Elastic collisions carried out in the radiofrequency-only collision cell of a triple quadrupole mass spectrometer have dramatic effects on the appearance of the mass spectra. The different cross sectional areas of the conformers allow preferential selection of one charge state distribution over the other on the basis of ion mobility. Preferential selection is dependent on the nature and pressure of the target gas as well as the nature of the protein. In the case of positively charged horse heart apomyoglobin (MW 16,951 da), a high charge state distribution centered around (M + 20H)²⁰⁺ predominates at low target gas pressures and a second distribution centered around (M + 10H)¹⁰⁺ predominates at high target gas pressures. Bimodal distributions are observed at intermediate pressures and, remarkably, charge states between the two distributions are not effectively populated under most of the conditions examined. Hard sphere collision calculations show large differences in collision frequencies and in the corresponding kinetic energy losses for the two conformational states and they demonstrate that the observed charge state selectivity can be explained through elastic collisions.     

A pulsed time-of-flight mass spectrometer for liquid secondary ion mass spectrometry

The design and performance of a new time-of-flight mass spectrometer is reported. The instrument combines the advantages of a pulsed drawout TOF analyzer with a liquid secondary ion source. Differences from commercially available pulsed TOF analyzers (Wiley/McLaren type) are discussed with regard to operation with ion desorption from a liquid matrix.     

High amplitude short time excitation: A method to form and detect low mass product ions in a quadrupole ion trap mass spectrometer

Collision induced dissociation (CID) in a quadrupole ion trap mass spectrometer using the conventional 30 ms activation time is compared with high amplitude short time excitation (HASTE) CID using 2 ms and 1 ms activation times. As a result of the shorter activation times, dissociation of the parent ions using the HASTE CID technique requires resonance excitation voltages greater than conventional CID. After activation, the rf trapping voltage is lowered to allow product ions below the low mass cut-off to be trapped. The HASTE CID spectra are notably different from those obtained using conventional CID and can include product ions below the low mass cut-off for the parent ions of interest. The MS/MS efficiencies of HASTE CID are not significantly different when compared with the conventional 30 ms CID. Similar results were obtained with a two-dimensional (linear) ion trap and a three-dimensional ion trap.     

Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer

We herein report upon an approach whereby the interpretation of tandem mass spectrometry spectra can be both expedited and simplified via the accurate mass assignment of product ions utilizing a tandem quadrupole time-of-flight mass spectrometer (QqTOF). The applicability of the QqTOF in the drug metabolism laboratory is illustrated by the elucidation and differentiation of the dissociative pathways for Bosentan and its hydroxylated and demethylated metabolites. Target analyte fragmentation mechanisms were readily achieved by the measurement of product ions with a mass accuracy <5 ppm, possible by single-point internal recalibration using the residual precursor ion as calibrant. Differentiation of both precursor and product ions from nominally isobaric matrix species derived from biological extracts is demonstrated by operation of the QqTOF at resolutions of 8000 (m/Δm_FWHM).     

Theoretical and numerical analysis of the behavior of ions injected into a quadrupole ion trap mass spectrometer

A numerical simulation method has been developed for the analysis of trapping ions injected into an ion trap mass spectrometer. This method was applied to clarify the effects of the following parameters on trapping efficiencies: (1) initial phase of the radio frequency (RF) drive voltage, (2) ion injection energy, and (3) RF peak voltage while injecting ions. The following conclusions were obtained by theoretical and simulation approaches. 1. The second and third dominant oscillations contribute significantly to the trapping mechanism of the injected ions, even for low q values. 2. A formula relating the operating parameters, which gives the maximum trapping efficiency, is derived. 3. Based on the above-mentioned formula, an advanced injection method is proposed, in which the RF peak voltage is decreased while injecting ions. The ability of this method to solve the problem of unequal sensitivity among different ion species is indicated by numerical simulation. Copyright 2000 John Wiley & Sons, Ltd.