Decay Mechanisms of Protonated 4-Quinolone Antibiotics After Electrospray Ionization and Ion Activation

作者：Borislav Kovačević, Pascal Schorr, Yulin Qi, Dietrich A. Volmer · 发表于：Journal of the American Society for Mass Spectrometry · 年份：2014 · DOI：10.1007/s13361-014-0972-2 · 被引用次数：33 · 研究领域：Mass Spectrometry Techniques and Applications、Analytical Chemistry and Chromatography、Microfluidic and Capillary Electrophoresis Applications

This study presents a detailed experimental investigation of charge isomers of protonated 4-quinolone antibiotics molecules formed during electrospray ionization (ESI) with proposed dissociation mechanisms after collisional activation. Piperazinyl quinolones have been previously shown to exhibit erratic behavior during tandem MS analyses of biological samples, which originated from varying ratios of two isomeric variants formed during ESI. Here, a combination of ESI-collision-induced dissociation (CID), differential ion mobility spectrometry (DMS), high resolution MS, and density functional theory (DFT) was used to investigate the underlying mechanisms of isomer formation and their individual dissociation behaviors. The study focused on ciprofloxacin; major findings were confirmed using structurally related 4-quinolones. DFT calculations showed a reversal of basicity for piperazinyl quinolones between liquid and gas phase. We provide an experimental comparison and theoretical treatment of factors influencing the formation ratio of the charge isomers during ESI, including solvent pH, protic/aprotic nature of solvent, and structural effects such as pK a and proton affinity. The actual dissociation mechanisms of the isomers of the protonated molecules were studied by separating the individual isomers via DMS-MS, which allowed type-specific CID spectra to be recorded. Both primary CID reactions of the two charge isomers originated from the same carboxyl group by charge-remote (CO...