Tandem mass spectrometric accurate mass performance of time-of-flight and Fourier transform ion cyclotron resonance mass spectrometry: a case study with pyridine derivatives (original) (raw)
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Rapid Communications in Mass Spectrometry, 2003
This article describes a simple method to perform lock mass corrected accurate mass measurements in tandem mass spectrometry (MS/MS) with a quadrupole time-of-flight (Q-TOF) mass spectrometer. The experimental approach consists of using the protonated molecule of a known compound, which is measured in a MS/MS function using low collision energy (no fragmentation), as mass calibrator. The unknown compound is acquired in MS/MS mode albeit using high collision energy. After the acquisition, the two MS/MS spectra of unknown and mass calibrator are combined, and the fragments of the unknown are lock mass corrected by using the protonated molecule of the mass calibrator. To prove this concept, 10 compounds were analyzed using this approach, the fragments interpreted and, where possible, related to structural data available in the literature. All the unequivocally assigned fragments were accurately mass measured with mass errors within appropriate limits, i.e. for m/z values <200 with a mass tolerance of 3 mDa while for m/z > 200 the mass tolerance is expressed as 10 ppm.
An introduction to quadrupole-time-of-flight mass spectrometry
Journal of Mass Spectrometry, 2001
A brief introduction is presented to the basic principles and application of a quadrupole-time-of-flight (TOF) tandem mass spectrometer. The main features of reflecting TOF instruments with orthogonal injection of ions are discussed. Their operation and performance are compared with those of triple quadrupoles with electrospray ionization and matrix-assisted laser desorption/ionization (MALDI) TOF mass spectrometers. Examples and recommendations are provided for all major operational modes: mass spectrometry (MS) and tandem MS (MS/MS), precursor ion scans and studies of non-covalent complexes. Basic algorithms for liquid chromatography/MS/MS automation are discussed and illustrated by two applications.
Rapid Communications in Mass Spectrometry, 2000
A matrix-assisted laser desorption/ionization (MALDI) source has been coupled to a tandem quadrupole/time-of-flight (QqTOF) mass spectrometer by means of a collisional damping interface. Mass resolving power of about 10,000 (FWHM) and accuracy in the range of 1 0 ppm are observed in both single-MS mode and MS/MS mode. Sub-femtomole sensitivity i s obtained in single-MS mode, and a few femtomoles in MS/MS mode. Both peptide mass mapping and CID analysis of tryptic peptides can be performed from the same MALDI target. Rapid spectral acquisition (a few seconds per spectrum) can be achieved in both modes, so high throughput protein identification is possible.
Rapid communications in mass spectrometry : RCM, 2012
Determining the elemental compositions of unknown molecules is an important goal of analytical chemistry. The isotope pattern revealed by a mass spectrometer provides valuable information regarding the elemental composition of a molecule. In order to employ spectral accuracy considerations for elemental composition determination, it is important to know how faithfully a mass spectrometer can record the isotope pattern and to understand the magnitude of the errors of the relative isotopic abundances. Twenty-four small molecule drugs and two natural products representing a diverse range of elemental compositions and ranging in molecular weight from 236 to 1663 Da were measured on a new hybrid orthogonal acceleration quadrupole time-of-flight (Q-TOF) mass spectrometer by flow infusion analysis. The similarity between the observed profile isotope pattern and the theoretical isotope pattern, denoted spectral accuracy, was calculated using a computational algorithm in the program MassWork...
Journal of Mass Spectrometry, 2006
The collision-induced dissociation (CID) mass spectra of several protonated benzylamines are described and mechanistically rationalized. Under collision-induced decomposition conditions, protonated dibenzylamine, for example, loses ammonia, thereby forming an ion of m/z 181. Deuterium labeling experiments confirmed that the additional proton transferred to the nitrogen atom during this loss of ammonia comes from the ortho positions of the phenyl rings and not from the benzylic methylene groups. A mechanism based on an initial elongation of a C-N bond at the charge center that eventually cleaves the C-N bond to form an ion/neutral complex of benzyl cation and benzylamine is proposed to rationalize the results. The complex then proceeds to dissociate in several different ways: (1) a direct dissociation to yield a benzyl cation observed at m/z 91; (2) an electrophilic attack by the benzyl cation within the complex on the phenyl ring of the benzylamine to remove a pair of electrons from the aromatic sextet to form an arenium ion, which either donates a ring proton (or deuteron when present) to the amino group forming a protonated amine, which undergoes a charge-driven heterolytic cleavage to eliminate ammonia (or benzylamine) forming a benzylbenzyl cation observed at m/z 181, or undergoes a charge-driven heterolytic cleavage to eliminate diphenylmethane and an immonium ion; and (3) a hydride abstraction from a methylene group of the neutral benzylamine to the benzylic cation to eliminate toluene and form a substituted immonium ion. Corresponding benzylamine and dibenzylamine losses observed in the spectra of protonated tribenzylamine and tetrabenzyl ammonium ion, respectively, indicate that the postulated mechanism can be widely applied. The postulated mechanisms enabled proper prediction of mass spectral fragments expected from protonated butenafine, an antifungal drug.
Journal of the American Society for Mass Spectrometry, 1999
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 Ͻ5 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 ϳ8000 (m/⌬m FWHM).
Rapid Communications in Mass Spectrometry, 2005
Atomic masses and isotopic abundances are independent and complementary properties for discriminating among ion compositions. The number of possible ion compositions is greatly reduced by accurately measuring exact masses of monoisotopic ions and the relative isotopic abundances (RIAs) of the ions greater in mass by þ1 Da and þ2 Da. When both properties are measured, a mass error limit of 6-10 mDa (<31 ppm at 320 Da) and an RIA error limit of 10% are generally adequate for determining unique ion compositions for precursor and fragment ions produced from small molecules (less than 320 Da in this study). 'Inherent interferences', i.e., mass peaks seen in the product ion mass spectrum of the monoisotopic [MþH] þ ion of an analyte that are À2, À1, þ1, or þ2 Da different in mass from monoisotopic fragment ion masses, distort measured RIAs. This problem is overcome using an ion correlation program to compare the numbers of atoms of each element in a precursor ion to the sum of those in each fragment ion and its corresponding neutral loss. Synergy occurs when accurate measurement of only one pair of þ1 Da and þ2 Da RIAs for the precursor ion or a fragment ion rejects all but one possible ion composition for that ion, thereby indirectly rejecting all but one fragment ion-neutral loss combination for other exact masses. A triplequadrupole mass spectrometer with accurate mass capability, using atmospheric pressure chemical ionization (APCI), was used to measure masses and RIAs of precursor and fragment ions. Nine chemicals were investigated as simulated unknowns. Mass accuracy and RIA accuracy were sufficient to determine unique compositions for all precursor ions and all but two of 40 fragment ions, and the two corresponding neutral losses. Interrogation of the chemical literature provided between one and three possible compounds for each of the nine analytes. This approach for identifying compounds compensates for the lack of commercial ESI and APCI mass spectral libraries, which precludes making tentative identifications based on spectral matches. Published in 2005 by John Wiley & Sons, Ltd. Each year 2800 high-volume production chemicals (those with annual production of at least 10 6 lbs) 1 and 87 000 commercially produced chemicals, 2 along with their synthetic precursors, byproducts, transformation products, and metabolites, ultimately enter waste streams. The ability to identify compounds not targeted by routine analytical methods is important for assessing risks posed to aquatic ecosystems and to human health. In addition, sabotage agents not included on target lists of analytical methods could pose identification problems. Mass spectrometry (MS) has been used extensively for structural elucidation of chemical compounds. Two independent physical properties distinguish among the MS ion compositions possible for a given nominal mass: the exact masses of ions and the relative isotopic abundances (RIAs) of ions greater in mass by 1 Da and 2 Da (in this work, these higher mass ions will refer to [MþHþ1] þ and [MþHþ2] þ ions) that arise from the presence of atoms of heavier stable isotopes of elements, e.g., 13 C, 2 H, 15 N, 17 O, 18 O, 33 S, 34 S, 37 Cl, and 81 Br. Ion composition elucidation (ICE) is a highresolution MS technique 3 that determines both exact masses and RIAs by acquiring selected ion recording (or multiple ion detection) data on a chromatographic elution time scale. Simultaneous measurement of the exact masses and RIAs of the þ1 Da and þ2 Da isotopic profiles increases by four-fold the upper mass limit of ions for which a unique elemental composition can be determined. 4 Over the last decade, ICE Published in 2005 by John Wiley & Sons, Ltd.
Molecules
Two scan modes of the triple quadrupole tandem mass spectrometer, namely Collision Induced Dissociation Precursor Ion scan and Neutral Loss scan, allow selectively pinpointing, in a complex mixture, compounds that feature specific chemical groups, which yield characteristic fragment ions or are lost as distinctive neutral fragments. This feature of the triple quadrupole tandem mass spectrometer allows the non-target screening of mixtures for classes of components. The effective (center-of-mass) energy to achieve specific fragmentation depends on the inter-quadrupole voltage (laboratory-frame collision energy) and on the masses of the precursor molecular ion and of the collision gas, through a non-linear relationship. Thus, in a class of homologous compounds, precursor ions activated at the same laboratory-frame collision energy face different center-of-mass collision energy, and therefore the same fragmentation channel operates with different degrees of efficiency. This article repo...
Internal energy deposition in chemical ionization/tandem mass spectrometry
Journal of the American Society for Mass Spectrometry, 2003
The efficiency of the collision-induced dissociation (CID) process as a function of the internal energy deposited into the ion during the ionization event was evaluated. (M ϩ H) ϩ ions of pyrrole, pyrrolidine, pyridine and piperidine (five and six-membered ring heterocyclics) were generated by chemical ionization (CI). The internal energy of the ions was varied by using different reagent gases. Both high-energy (keV) and low-energy (eV) CID were performed on these ions. The experiments showed that the (M ϩ H) ϩ ions of the five-membered ring compounds, pyrrole and pyrrolidine, have higher fragmentation efficiencies than the sixmembered ring compounds, pyridine and piperidine. Fragmentation efficiencies in highenergy CID clearly correlate with the internal energy deposited by the ionization technique. Experiments showed that the low-energy CID process is more sensitive than high-energy CID