Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN, 47405, USA.
Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN, 55455, USA.
J Am Soc Mass Spectrom. 2019 Aug;30(8):1464-1480. doi: 10.1007/s13361-019-02210-w. Epub 2019 Apr 16.
The 14- and 16-membered macrolide antibiotics are an important structural class. Ubiquitously produced by a number of bacterial strains, namely actinomycetes, purification and structure elucidation of the wide array of analogs is challenging, both for discovery efforts and methodologies to monitor for byproducts, metabolites, and contaminants. Collision-induced dissociation mass spectrometry offers an attractive solution, enabling characterization of mixtures, and providing a wealth of structural information. However, interpretation of these spectra can be difficult. We present a study of 14- and 16-membered macrolide antibiotics, including MS analysis for unprecedented depth of coverage, and complimentary analysis with DO and HO labeling to elucidate fragmentation mechanisms. These analyses contrast the behaviors of varying classes of macrolides and highlight how analogues can be identified in relation to similar structures, which will provide utility for future studies of novel macrolides, as well as impurities, metabolites, and degradation products of pharmaceuticals. Graphical Abstract.
14 元和 16 元大环内酯类抗生素是一个重要的结构类别。许多细菌菌株（即放线菌）普遍产生这些抗生素，因此，广泛的类似物的纯化和结构阐明既具有挑战性，又需要用于发现副产品、代谢物和污染物的方法。碰撞诱导解离质谱分析提供了一种有吸引力的解决方案，能够对混合物进行特征描述，并提供丰富的结构信息。然而，这些光谱的解释可能很困难。我们对 14 元和 16 元大环内酯类抗生素进行了研究，包括前所未有的深度覆盖的 MS 分析，以及与 DO 和 HO 标记的互补分析，以阐明碎裂机制。这些分析对比了不同类别大环内酯类抗生素的行为，并强调了如何根据类似结构识别类似物，这将为未来对新型大环内酯类抗生素以及药物的杂质、代谢物和降解产物的研究提供实用性。
