Scott A. McLuckey

Mass spectrometry/mass spectrometry : techniques and applications of Tandem mass spectrometry

Introduction to mass spectrometry/mass spectrometry - history of mass spectrometry/mass spectrometry, concepts and principles, nomenclature MS/MS instrumentation - principles of charged-particle analysis, sector-based MS/MS instruments, quadrupole instruments, hybrid instruments, MS/MS with ion-trapping techniques, reaction regions reactions in MS/MS - unimolecular dissociation, activation reactions reactive collisions, charge permutation reactions applications of MS/MS to fundamental studies - ion structures, reaction meachanisms, thermochemistry characteristics of MS/MS for analytical applications - sample considertions, choice of ionization method, interpretation of MS/MS spectra analytical applications - environmental applications, natural products applications, industrial products applications, foods and flavours applications, forensic chemistry applications, petroleum and petroleum products applications, bioorganic applications, pharmaceutical applications, applications to continuos flow samples and processes conclusions and outlook - instrumentation in MS/MS, outlook for advanced applications, interpretation of MS/MS data, conclusions. Appendices: MS/MS scan modes on various instrument configurations frequently used symbols and acronyms.

Tandem Mass Spectrometry of Small, Multiply Charged Oligonucleotides

Multiply charged anions derived from electrospray ionization of the sodium salts of various small oligonucleotides (n = 4−8) have been subjected to tandem mass spectrometry (MS/MS) in a quadrupole ion trap. All ions were observed to dissociate with high efficiencies even under conditions not ordinarily conducive for the observance of high MS/MS efficiency. Large fractions of the total product ion signal could be attributed to single-cleavage reactions with the parent ion charge shared among the two product ions in various combinations. In every case, the most facile reaction was observed to be the loss of the adenine anion. This reaction was then observed to be followed by cleavage of the 3′ C–O bond of phosphodiester linkage of the sugar from which the adenine had been lost.

SPECIAL FEATURE:TUTORIAL Slow Heating Methods in Tandem Mass Spectrometry

Several approaches to ion activation in tandem mass spectrometry have been developed in recent years for use in ion trapping instruments that allow for conditions to be reached wherein rates of ion activation and deactivation are comparable. These approaches are defined as slow heating methods and include continuous-wave laser infrared multiphoton dissociation, dissociation driven by blackbody radiation, quadrupole ion trap collisional activation and sustained off-resonance irradiation in ion cyclotron resonance mass spectrometry. In the limiting case in which ion activation and deactivation rates are equal, a steady-state parent ion internal energy distribution is achieved and the kinetics of dissociation can be interpreted in analogy with thermal dissociation. This discussion describes the thermal analogy and the limiting conditions of rapid energy exchange and slow energy exchange along with the possible ramifications for dissociation rates and product ion spectra. The figures of merit that the various slow heating methods share as a class of activation methods are also discussed. The purpose of this perspective is to provide a frame-of-reference from which slow heating methods can be considered. Such methods are seeing increasing use as the number of ion trapping instruments grows and have shown remarkable success with dissociation of high-mass ions.

Principles of collisional activation in analytical mass spectrometry.

Collisional activation has played an essential role in the development of mass spectrometry/mass spectrometry (MS/MS). It was the first activation method to be employed and continues to be by far the most widely used. As instrumentation for MS/MS has evolved it has been found that collisional activation can be effected under a remarkably wide range of conditions for a wide range of ions. It is fair to conclude from the growth of MS/MS over the past fifteen years that collisional activation has been spectacularly successful. However, it has limitations. As a community, we have learned much over the years regarding these limitations both from empirical and fundamental points of view. This overview provides background on the development of collisional activation and discusses the importance of the interaction potential and timing on mechanisms for energy transfer. Parts of the discussion is devoted to changing reference frames from the laboratory to the center of mass to simplify visualizing what is possible and what is probable in collisional activation.

Collision‐Induced Dissociation (CID) of Peptides and Proteins

The most commonly used activation method in the tandem mass spectrometry (MS) of peptides and proteins is energetic collisions with a neutral target gas. The overall process of collisional activation followed by fragmentation of the ion is commonly referred to as collision-induced dissociation (CID). The structural information that results from CID of a peptide or protein ion is highly dependent on the conditions used to effect CID. These include, for example, the relative translational energy of the ion and target, the nature of the target, the number of collisions that is likely to take place, and the observation window of the apparatus. This chapter summarizes the key experimental parameters in the CID of peptide and protein ions, as well as the conditions that tend to prevail in the most commonly employed tandem mass spectrometers.

Ion trap mass spectrometry

The quadrupole ion trap is a mass spectrometer whose essential components can be held in one hand. But it has a mass range of about 105 daltons per charge, provides molecular weight and structural information on biopolymers, and has the greatest sensitivity of all mass spectrometers. These features, however, have become available only within the past few years. They stem from an almost neglected 1958 invention, one in which interest was maintained by only a few research groups, notably those of John Todd at the University of Kent in England and Ray March at Trent University in Canada. Development of a new scanning method by George Stafford and his coworkers of Finnigan Corp. provided the impetus that led Finnigan to introduce a commercial ion trap in 1983. Since then, the device has been transformed from a simple gas chromatography detector to a high-performance mass spectrometer. In the late 1950s, Wolfgang Paul and his coworkers at ...

Ion isolation and sequential stages of mass spectrometry in a quadrupole ion trap mass spectrometer

Sequential reactions with as many as eleven steps (MS12) are accomplished with a quadrupole ion trap mass spectrometer. Both collision induced dissociation and ion/molecule reactions can be utilized in these reaction sequences. The isolation of intermediate products is performed extremely rapidly through the application of a combination of d.c. and r.f. potentials to give, to the ions of interest, coordinates near a cusp of the stability diagram (az = 0.150, qz = 0.781). The ion yields and signal-to-noise (S/N) ratios can be quite high for each individual step, resulting in good ultimate yields and S/N ratios even after multiple reaction steps. The scan functions used are investigated in detail by exploring the ejection of xenon isotopes in experiments which reveal the shape of the stability diagram in the cusp region. The resolution of the isolation procedure is investigated. These ion isolation capabilities are applied in a series of steps to cause extensive dissociation of the saturated sterane, cholestane, to yield a stable aromatic ion, C6H+5, and to demonstrate that the m/z 79 fragment of dimethylpyrrole is protonated benzene. They also allow multiple charge exchange and dissociation reactions to be performed in sequence on a single population of molecular ions.

Ion trap tandem mass spectrometry applied to small multiply charged oligonucleotides with a modified base

Two isomeric oligodeoxynucleotide hexamers, 5′-d(N-6meATGCAT)-3′ and 5′-d(ATGSmeCAT)-3′, were subjected to analysis by electrospray and ion trap mass spectrometry. In the case of the isomer with a modified adenine, location of the modified base in the sequence was straightforward and a triple mass spectrometry experiment provided information on the identity of the modification. In contrast, the isomer with the methylated cytosine did not yield definitive information on the location or identity of the modification. Tandem mass spectrometry data in this case could indicate that the modification was present on either the third or fourth nucleoside. The two isomers represent extremes in the facility with which modified bases can be identified and located in a small oligonucleotide via multiple mass spectrometry of multiply charged anions. A preference for loss of particular bases strongly influences which structurally diagnostic ions are formed upon collisional activation. The likelihood for locating and identifying a modified base is dependent, therefore, upon the likelihood that the base is lost directly from the parention.

Kinetic energy effects in mass spectrometry/mass spectrometry using a sector/quadrupole tandem instrument

Abstract Using a new hybrid (magnet/quadrupole) tandem mass spectrometer the effects of ion kinetic energy and target mass upon energy deposition have been investigated. In the range 1–100 eV, the degree of fragmentation is very sensitive to changes in the translational energy of the parent ion. Comparisons with MS/MS spectra recorded for the same ions (protonated 5-indanol, protonated diethylamine) using other instruments show that less significant changes in spectra occur in the kV energy range. Plots of branching ratios for competitive collision-induced dissociation channels against collision energy (1–100 eV) resemble, qualitatively, breakdown curves displaying ion abundances versus internal energy. In addition, comparisons of the effect of collision energy are made with spectral changes resulting from selection of the scattering angle in kV energy collisions. It is evident that translational energy selection is a counterpart, for spectrometers operating at low translational energy, of angle-resolved mass spectrometry.

Coupling of an atmospheric-samling ion source with an ion-trap mass spectrometer☆

Abstract An atomospheric-sampling glow-discharge ionization source has been interfaced with an ion-trap mass spectrometer. Under optimum conditions, the efficiency of ion injection is 1–5%. Several factors have a significant effect on the ion injection efficiency, including the voltages on the three-element lens system situated between the ion-source exit and the ion-trap entrance end-cap, the pressure of the bath gas present in the ion-trap vacuum housing, the nature of the bath gas and the amplitude of the radiofrequency voltage applied to the ring electrode during ion injection. Collision-induced dissociation (and electron detachment from anions) is also observed for some ions on injection, depending on the conditions. The most important experimental variables in determining the extent to which dissociation (or electron detachment) occurs are the nature of the bath gas, the bath gas presure and the radiofrequency voltage applied to the ring electrode during injection. These effects are illustrated with data obtained for polyatomic anions injected from the golw-discharge ion source.