Abstract
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/Δ FWHM).
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References
Gelpi, E. J. Chromatogr. 1995, 32, 59.
Yu, X.; Cui, D.; Davis, M. R. J. Am. Soc. Mass Spectrom. 1999, 10, 175.
Fernandez-Metzler, C. L.; Owens, K. G.; Baillie, T. A.; King, R. C. Drug Metab. Dispo 1999, 27, 32.
Morris, H. R.; Paxton, T.; Dell, A.; Langhorne, J.; Berg, M.; Bordoli, R. S.; Hoyes, J.; Bareman, R. H. Rapid Commun. Mass Spectrom. 1996, 10, 889.
Shevchenko, A.; Chernushevich, I.; Ens, W.; Standing, K. G.; Thompson, B.; Wilm, M.; Mann, M. Rapid Commun. Mass Spectrom. 1997, 11, 1015.
Cotter, R. J. Time-of-Flight Mass Spectrometry: Instrumentation and Applications in Biological Research ACS Professional Reference Books: Washington, DC, 1997.
Verentchikov, A. N.; Ens, W.; Standing, K. G. Anal. Chem. 1994, 66, 126.
Chernushevich, I. V.; Ens, W.; Standing, K. G. In Electrospray Ionization Mass Spectrometry; Cole, R. B., Ed.; Wiley—Interscience: New York, 1997.
March, R. E. Int. J. Mass Spectrom. Ion Processes 1992, 118/119, 71.
Hopfgartner, G.; Vetter, W.; Meister, W.; Ramuz, H. J. Mass Spectrom. 1996, 31, 69.
Thomson, B. A.; Douglas, D. J.; Corr, J. J.; Hager, J. W.; Jolliffe, C. L. Anal. Chem. 1995, 67, 1696.
Krutchinsky, A. N.; Chernushevich, I. V.; Spicer, V. L.; Ens, W.; Standing, K. G. J. Am. Soc. Mass Spectrom. 1998, 9, 569.
Blom, K. F. J. Am. Soc. Mass Spectrom. 1998, 9, 789.
Barbacci, D. C.; Russell, D. H.; Schultz, J. A.; Holocek, J.; Ulrich, S.; Burton, W.; Stipdonk, M. Van J. Am. Soc. Mass Spectrom. 1998, 9, 1328.
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Hopfgartner, G., Chernushevich, I.V., Covey, T. et al. Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer. J Am Soc Mass Spectrom 10, 1305–1314 (1999). https://doi.org/10.1016/S1044-0305(99)00097-5
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DOI: https://doi.org/10.1016/S1044-0305(99)00097-5