Mass spectrometry imaging of levofloxacin distribution in TB-infected pulmonary lesions by MALDI-MSI and continuous liquid microjunction surface sampling

• Published in: International journal of mass spectrometry Vol. 377; pp. 699 - 708
• Main Authors: Prideaux, Brendan, ElNaggar, Mariam S., Zimmerman, Matthew, Wiseman, Justin M., Li, Xiaohua, Dartois, Véronique
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2015
• Subjects: Flowprobe; Imaging; MALDI-MSI; Pharmacokinetics; Tuberculosis; Tuberculosis; Flowprobe; MALDI-MSI; Pharmacokinetics; Imaging
• ISSN: 1387-3806; 1873-2798
• DOI: 10.1016/j.ijms.2014.08.024

[Display omitted] •MALDI-MSI and flowprobe ESI-MS have been applied to localize levofloxacin in tissue.•Flowprobe was utilized for tissue profiling and imaging.•Both technologies provided intra-lesion drug partitioning information.•Flowprobe is a suitable alternative to MALDI when high resolution is not required. A multi-modal mass spectrometry imaging (MSI) and profiling approach has been applied to assess the partitioning of the anti-TB fluoroquinolone levofloxacin into pulmonary lesions. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and a commercial liquid microjunction surface sampling technology (LMJ-SSP), or flowprobe, have been used to both spatially profile and image drug distributions in lung tissue sections from TB-infected rabbits following oral administration of a single human-equivalent dose. Levofloxacin levels were highest at 6h post-dose in normal lung, cellular granuloma, and necrotic caseum compartments. The drug accumulated in the cellular granuloma regions with lower amounts partitioning into central caseous compartments. Flowprobe imaging at 630μm (limited by the probe tip diameter) enabled visualization of drug distribution into lesion compartments, including limited differentiation of relative drug abundance in cellular versus caseous regions of the lesions. MALDI-MSI analysis at 75μm provided more detailed drug distribution, which clearly accumulated in the cellular region immediately surrounding the central caseum core. Imaging and profiling data acquired by flowprobe and MALDI-MSI were validated by quantitative LC/MS/MS analysis of lung and granuloma homogenates taken from the same animals. The results of the investigation show flowprobe imaging and sampling as a rapid and sensitive alternative to MALDI-MSI for profiling drug distributions into tissues when spatial resolution of data below the threshold of the probe diameter is not required.