Department of Chemistry - BMC, Uppsala University, 75123 Uppsala, Sweden.
Anal Chem. 2023 Dec 5;95(48):17843-17850. doi: 10.1021/acs.analchem.3c03931. Epub 2023 Nov 16.
Identifying and mapping steroids in tissues can provide opportunities for biomarker discovery, the interrogation of disease progression, and new therapeutics. Although separation coupled to mass spectrometry (MS) has emerged as a powerful tool for studying steroids, imaging and annotating steroid isomers remains challenging. Herein, we present a new method based on the fragmentation of silver-cationized steroids in tandem MS, which produces distinctive and consistent fragmentation patterns conferring confidence in steroid annotation at the regioisomeric level without using prior derivatization, separation, or instrumental modification. In addition to predicting the structure of the steroid with isomeric specificity, the method is simple, flexible, and inexpensive, suggesting that the wider community will easily adapt to it. We demonstrate the utility of our approach by visualizing steroids and steroid isomer distributions in mouse brain tissue using silver-doped pneumatically assisted nanospray desorption electrospray ionization mass spectrometry imaging.
鉴定和绘制组织中的类固醇可以为生物标志物的发现、疾病进展的探究以及新疗法的发展提供机会。尽管与质谱（MS）相结合的分离已成为研究类固醇的有力工具，但对类固醇异构体的成像和注释仍然具有挑战性。在此，我们提出了一种新方法，基于串联 MS 中银离子化类固醇的断裂，产生独特且一致的断裂模式，从而在不使用衍生化、分离或仪器修改的情况下，在区域异构体水平上对类固醇注释提供信心。除了具有异构体特异性预测类固醇结构外，该方法还简单、灵活且廉价，表明更广泛的社区将很容易适应它。我们通过使用银掺杂气动辅助纳米喷雾解吸电喷雾电离质谱成像在小鼠脑组织中可视化类固醇和类固醇异构体分布，证明了我们方法的实用性。
