Published:Journal of Chromatographic Science,
ISSN 0021-9665Volume
40, Number 10, November/December 2002, pp. 538-549
Thin-Layer Chromatography—Postsource-Decay Matrix-Assisted
Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Small Drug Molecules
Anna Crecelius and Malcolm R. Clench
Biomedical Research Centre, School of Science and Mathematics, Sheffield Hallam
University, Pond Street, Sheffield, U.K.
Don S. Richards
Pfizer Global R&D, Ramsgate Road, Sandwich, Kent, U.K.
David Evason and Vic Parr
SAI Ltd, New Elm Lane, Manchester, U.K.
The structural analysis of small drug molecules by directly coupling
thin-layer chromatography (TLC) with postsource-decay (PSD) matrix-assisted
laser desorption/ionization (MALDI) mass spectrometry is reported. The applicability
of this technique is shown using two examples: the TLC–PSD MALDI analysis
of two representatives of nonsteroidal antiinflammatory drugs (tenoxicam and
piroxicam) and the analysis of the pharmaceutically active compound UK-137,457
and one of its related substances UK-124,912. The matrices a-cyano-4-hydroxycinnamic
acid (a-CHCA) and graphite are used to investigate the effect of the precursor
ion selection on the TLC–PSD MALDI spectra of the drug molecules studied.
Although a-CHCA enhances the [M+H]+ ion formation graphite produces in general
only sodium adducts. Structural differentiation of tenoxicam and piroxicam is
possible only by selecting the sodium adduct of both drug molecules as precursor
ions. In the case of the TLC–PSD MALDI analysis of UK-137,457 and its
related substance UK-124,912 at the 1% level, the PSD spectra obtained in a-CHCA
by selecting the protonated adduct of the small molecules as precursor ions
shows distinguishable dissociation patterns containing structurally significant
information.
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