Matrix-assisted laser desorption/ionization-ion mobility separation-mass spectrometry imaging of vinblastine in whole body tissue sections.
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.
Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK.
Paul J
PJ
Trim
Claire M
CM
Henson
Jennie L
JL
Avery
Andrew
A
McEwen
Marten F
MF
Snel
Emmanuelle
E
Claude
Peter S
PS
Marshall
Andrew
A
West
Alessandra P
AP
Princivalle
Malcolm R
MR
Clench
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014018:Tissue Distribution; D014747:Vinblastine / Q000032:analysis* / Q000493:pharmacokinetics*; D015262:Xenobiotics / Q000032:analysis / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D015262:Xenobiotics; D014747:Vinblastine