Exact mass measurement

The mass spectral fragmentations of 9,10-dimethoxy-2,3,4,6,7,ll/)-hexa-hydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140 and -2,4-diones 141, under electron ionization (at 70 eV) were examined by metastable ion analysis, a collosion-induced dissociation technique and exact mass measurement (97RCM1879). Methyl substituent on N(3) in 140 (R = Me) had a larger effect on both the fragmentation and on the peak intensities, than a methyl substituent on C(6) (R = Me). The ionized molecules of 140 (R = H) were rather stable, whereas 4-phenyl substitution on C(4) of 140 (R = Ph) promoted the fragmentations of the molecular ions. The hexahydro-1//-pyrimido[6,l-n]isoquinoline-2,4-diones 141 were more stable, than the hexahydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140, and the molecular ions formed base peaks. 

Figure 5.45 Structures of (1) Bosentan (C27H29N5O6S [M + H]+ 552.1917) and three of its metabolites, formed by (2) oxidation (C27H29N5O7S [M + H]+ 568.1866), (3) demethylation (C26H27N5O6S [M- -H]+ 538.1760), and (4) demethylation-oxidation (C26H27N5O7S [M + M]+ 554.1709). Reprinted by permission of Elsevier Science from Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer , by Hopfgartner, G., Chemushevich, I. V., Covey, T., Plomley, 1. B. and Bonner, R., Journal of the American Society for Mass Spectrometry, Vol. 10, pp. 1305-1314, Copyright 1999 by the American Society for Mass Spectrometry.

Resolution does not affect the accuracy of the individual accurate mass measurements when no separation problem exists. When performing accurate mass measurements on a given component in a mixture, it may be necessary to raise the resolution of the mass spectrometer wherever possible. Atomic composition mass spectrometry (AC-MS) is a powerful technique for chemical structure identification or confirmation, which requires double-focusing magnetic, Fourier-transform ion-cyclotron resonance (FTICR) or else ToF-MS spectrometers, and use of a suitable reference material. The most common reference materials for accurate mass measurements are perfluorokerosene (PFK), perfluorotetrabutylamine (PFTBA) and decafluorotriph-enylphosphine (DFTPP). One of the difficulties of high-mass MS is the lack of suitable calibration standards. Reference inlets to the ion source facilitate exact mass measurement. When appropriately calibrated, ToF mass... 

TLC-Raman laser microscopy (X = 514 nm) in conjunction with other techniques (IR microscopy, XRF and HPLC-DAD-ESI-MS) has been used in the analysis of a yellow impurity in styrene attributed to reaction of the polymerisation inhibitor r-butylcatechol (TBC) and ammonia (from a washing step) [795]. Although TLC-FT-Raman did not allow full structural characterisation, several structural elements were identified. Exact mass measurement indicated a C20H25O3N compound which was further structurally characterised by 1H and 13C NMR. 

Valproic acid was quite volatile and vaporized as soon as it was admitted to the source of the mass spectrometer. Only a very weak ion was detectable in the molecular ion region at m/e 145. This would correspond to (M3-H)+, but exact mass measurement was not possible because of the peak s small size and the short lifetime of the sample in the mass spectrometer. 

K. Biemann, Utility of exact mass measurements, Methods in Enyzmo-logy, 193 (1990) 295-305. 

K.L. Busch, Using exact mass measurements, Spectroscopy, 9(7) (1994) 21-22. 

T. Storm, C. Hartig, T. Reemtsma and M. Jekel, Exact mass measurements on-line with high-performance liquid chromatography on a quadrupole mass spectrometer. Anal. Chem., 73 (2001) 589-595. 

Busch, K.L. The Resurgence of Exact Mass Measurement with FTMS. Spectroscopy 2000,15. 22-27. 

Hopfgartner, G. Chemushevich, I.V. Covey, T. Plomley, J.B. Bonner, R. Exact Mass Measurement of Product Ions for the Structural Elucidation of Drug Metabolites With a Tandem Quad-rupole oaTOF Mass Spectrometer. J. Am. Soc. Mass Spectrom. 1999, 10, 1305-1314. 

Haas, M.J. Fully Automated Exact Mass Measurements by High-Resolution ESI on a Sector Instrament. Rapid Commun. Mass Spectrom. 1999, 73,381-383. 

Hopfgartner, G. Chernushevich, I. V. Covey, T Plomley, J. B. Bonner, R. Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem... 

Instrumental screening methods based on exact mass measures have increased for multiscreening purposes offering adequate uncertainty and possible identification of nontarget compounds. On the other hand, biological approaches offer as well another possibility for rapid and cost-effective alternative. 

As the ion source pressure rises, ion-molecule reactions become possible, sample ions reacting with sample molecules. In the case of exact mass measurement, reaction can occur with the PFK mass reference 126). The observed reactions in the mass spectrum of ruthen-nium porphyrincarbonyl, yielding ions of the type [M-CO -h C, F2n] n = 1-4), illustrate this problem. Similarly, in the spectrum of Ni(PF3)4 ion-molecule reactions result in species such as Ni2(PF3) + n = 2-5) and Ni2(PF)2(PF3)m (m = 2-4) and, in the (CO)5CrC(CH3)OCH3 system, reactions of the following type are observed 127). 

Exact mass measurement at high resolution is an important tool along with other spectroscopic methods to help confirm the structure of novel flavonoids. It is used as structural proof when elemental analysis is not possible, e.g., when studying minor components. When EI-MS can be used, 1 to 10 pmol samples are required for one measurement however, when FAB-MS is used, 0.1 to 1 nmol is normally required. The use of ESI on a double focusing mass spectrometers and MALDI-TOF-MS requires smaller amounts of sample, and subpi-comole amounts of flavonoids may be adequate. 

Mass range up to 7000 Da. Exact mass measurements are usually done by peak matching. The accuracy of the mass is the same as obtained in El, Cl. Relatively low sensitivity. Molecular ions often absent High mass range. Sample amount very low (picomoles or less). Mass accuracy (0.1 to 0.01%) is normally not as high as for other mass spectrometry methods. 

Static FAB/LSIMS provides a continuous signal for chlorophylls and their derivatives so that exact mass measurements may be carried out to determine elemental compositions, or tandem mass spectra following CID may be recorded. 

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