UNASSIGNED: Colistin and @entity6414 are effective treatment options for Gram-negative resistant bacteria but are used as last-line therapy due to their dose-limiting nephrotoxicity. A critical factor in developing safer polymyxin analogues is understanding accumulation of the drugs and their metabolites, which is currently limited due to the lack of effective techniques for analysis of these challenging molecules. @entity2996 ( @entity2996 ) allows direct detection of targets (drugs, metabolites, and endogenous compounds) from tissue sections. The presented study exemplifies the utility of @entity2996 by measuring the distribution of @entity69934 , colistin, and @entity6414 nonapeptide ( @entity69935 ) within dosed @entity35 kidney tissue sections. The label-free @entity2996 analysis revealed that the nephrotoxic compounds (polymyxin B1 and @entity3273 ) preferentially accumulated in the renal cortical region. The less nephrotoxic analogue, @entity69935 , was more uniformly distributed throughout the kidney. In addition, metabolites of the dosed compounds were detected by @entity2996 . Kidney homogenates were analyzed using LC/MS/MS to determine total drug exposure and for metabolite identification. To our knowledge, this is the first time such techniques have been utilized to measure the distribution of @entity3272 drugs and their metabolites. By simultaneously detecting the distribution of drug and drug metabolites, @entity2996 offers a powerful alternative to tissue homogenization analysis and label or antibody-based imaging.

Investigating Nephrotoxicity of XXXX Derivatives by Mapping Renal Distribution Using Mass Spectrometry Imaging.

@entity3273 :: ('MESH:D003091', 'Chemical') :: ['colistin'] @entity69935 :: ('MESH:C038934', 'Chemical') :: ['polymyxin B nonapeptide', 'PMBN'] @entity6414 :: ('MESH:D011112', 'Chemical') :: ['polymyxin B'] @entity3272 :: ('MESH:D011113', 'Chemical') :: ['polymyxin'] @entity2996 :: ('MESH:C564543', 'Disease') :: ['Mass spectrometry imaging', 'MSI'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity69934 :: ('MESH:C121746', 'Chemical') :: ['polymyxin B1']
@entity3272 :: (MESH:D011113,Chemical) :: ['Polymyxin']
