Crecelius Anna, Clench Malcolm R, Richards Don S, Evason David, Parr Vic
Biomedical Research Centre, School of Science and Mathematics, Sheffield Hallam University, Pond Street, Sheffield, UK.
J Chromatogr Sci. 2002 Nov-Dec;40(10):614-20. doi: 10.1093/chromsci/40.10.614.
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 alpha-cyano-4-hydroxycinnamic acid (alpha-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 alpha-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 alpha-CHCA by selecting the protonated adduct of the small molecules as precursor ions shows distinguishable dissociation patterns containing structurally significant information.
报道了通过将薄层色谱（TLC）与源后衰变（PSD）基质辅助激光解吸/电离（MALDI）质谱直接联用对小分子药物进行结构分析。通过两个例子展示了该技术的适用性：对两种非甾体抗炎药（替诺昔康和吡罗昔康）进行TLC-PSD MALDI分析，以及对药物活性化合物UK-137,457及其相关物质之一UK-124,912进行分析。使用α-氰基-4-羟基肉桂酸（α-CHCA）和石墨作为基质，研究前体离子选择对所研究药物分子的TLC-PSD MALDI谱图的影响。尽管α-CHCA能增强[M+H]+离子的形成，但石墨通常只产生钠加合物。只有通过选择两种药物分子的钠加合物作为前体离子，才能区分替诺昔康和吡罗昔康的结构。在对UK-137,457及其相关物质UK-124,912进行1%水平的TLC-PSD MALDI分析时，通过选择小分子的质子化加合物作为前体离子，在α-CHCA中获得的PSD谱图显示出包含结构重要信息的可区分的解离模式。
