Matrix-Assisted Laser Desorption/Ionization-Ion Mobility Separation-Mass Spectrometry Imaging of Vinblastine in Whole Body Tissue Sections

Abstract

During early-stage drug development, drug and metabolite distribution studies are carried out in animal tissues using a range of techniques, particularly whole body autoradiography (WBA). While widely employed, WBA has a number of limitations, including the following: expensive synthesis of radiolabeled drugs and analyte specificity and identification. WBA only images the radiolabel. MALDI MSI has been shown previously to be advantageous for imaging the distribution of a range of drugs and metabolites in whole body sections. Ion mobility separation (IMS) adds a further separation step to imaging experiments; demonstrated here is MALDI-IMS-MS whole body imaging of rats dosed at 6 mg/kg i.v. with an anticancer drug, vinblastine and shown is the distribution of the precursor ion m/z 811.4 and several product ions including m/z 793, 751, 733, 719, 691, 649, 524, and 355. The distribution of vinblastine within the ventricles of the brain is also depicted. Clearly demonstrated in these data are the removal of interfering isobaric ions within the images of m/z 811.4 and also of the transition m/z 811-751, resulting in a higher confidence in the imaging data. Within this work, IMS has shown to be advantageous in both MS and MS/MS imaging experiments by separating vinblastine from an endogenous isobaric lipid.

MALDI In-Source Decay, from Sequencing to Imaging

“…For small molecules analysis, two main classes may be distinguished -exogenous drugs and endogenous metabolites. Exogenous drugs have been studied in MALDI-MSI far later than proteins (since 2004) for different targets such as olanzapine (antipsychotic) [85][86][87], imatinib [87], vinblastine [88], and banoxantrone [89] (cancer drugs). Among endogenous metabolites, lipids such as glycerophospholipids and glycosphingolipids or simple lipids like cholesterol, diacylglycerols, or triacylglycerols have been extensively investigated [90].…”

Microscope mode secondary ion mass spectrometry imaging with a Timepix detector

“…[8][9][10] Disease studies such as the fundamental understanding of the biochemistry of neurodegenerative diseases 11,12 or cancer, 13 drug distribution studies 10,14 and forensics, 15,16 among others, also benefit from the information revealed by MSI.…”

Ion Mobility in Clinical Analysis: Current Progress and Future Perspectives

“…Coupling MSI with preseparation by IMS has allowed marked enhancement of imaging contrast through improved selectivity and signal-to-noise ratio by separating isobaric interferences. MALDI-IM-MSI was shown to expand the dimensionality of data produced, in comparison with traditional MALDI-MSI data sets, for human glioma studies (47 ) and was also used for imaging of the anticancer drug vinblastine in whole body tissues (48 ). Fig.…”