Assaf Jaber, Kollmeier Annette Sophie, Müller Christian, Parr Maria Kristina
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Fabeckstr. 34-36, 14195, Berlin, Germany.
Rapid Commun Mass Spectrom. 2019 Jan 30;33(2):215-228. doi: 10.1002/rcm.8313.
In various fields of chemical analyses, structurally unknown analytes are considered. Proper structure confirmation may be challenged by the low amounts of analytes that are available, e.g. in early stage drug development, in metabolism studies, in toxicology or in environmental analyses. In these cases, mass spectrometric techniques are often used to build up structure proposals for these unknowns. Fragmentation reactions in mass spectrometry are known to follow definite pathways that may help to assign structural elements by fragment ion recognition. This work illustrates an investigation of fragmentation reactions for gas chromatography/electron ionization mass spectrometric characterization of benzophenone derivatives using the analgesic drug ketoprofen and seven of its related compounds as model compounds.
Deuteration and O-labelling experiments along with high-resolution accurate mass and tandem mass spectrometry (MS/MS) were used to further elucidate fragmentation pathways and to substantiate rationales for structure assignments. Low-energy ionization was investigated to increase confidence in the identity of the molecular ion.
The high-resolution mass analyses yielded unexpected differences that led to reconsideration of the proposals. Site-specific isotopic labelling helped to directly trace back fragment ions to their respective structural elements. The proposed fragmentation pathways were substantiated by MS/MS experiments.
The described method may offer a perspective to increase the level of confidence in unknown analyses, where reference material is not (yet) available.
在化学分析的各个领域，都会考虑结构未知的分析物。适当的结构确证可能会受到可用分析物量少的挑战，例如在药物研发早期、代谢研究、毒理学或环境分析中。在这些情况下，质谱技术常被用于构建这些未知物的结构推测。已知质谱中的碎裂反应遵循特定途径，这有助于通过碎片离子识别来确定结构元素。这项工作展示了以镇痛药酮洛芬及其七种相关化合物作为模型化合物，对二苯甲酮衍生物进行气相色谱/电子电离质谱表征时碎裂反应的研究。
采用氘代和O标记实验，结合高分辨精确质量和串联质谱（MS/MS），进一步阐明碎裂途径并证实结构归属的原理。研究了低能电离以增强对分子离子身份的信心。
高分辨质量分析产生了意想不到的差异，这导致对推测进行重新考虑。位点特异性同位素标记有助于直接将碎片离子追溯到其各自的结构元素。MS/MS实验证实了所提出的碎裂途径。
所描述的方法可能为在尚无（或尚未有）参考物质的未知分析中提高置信水平提供一个视角。
