On‐tissue chemical derivatization of 3‐methoxysalicylamine for MALDI‐imaging mass spectrometry

Abstract

MALDI-imaging mass spectrometry (IMS) has been shown to be a powerful tool to study drug distributions in organ tissue as well as whole animal bodies. Nevertheless, not all drugs are amenable to MALDI while others may be limited by poor sensitivity poor sensitivity. The use of chemical derivatization to improve detection of small molecules by mass spectrometry techniques is well documented. To our knowledge, however, this approach has not been applied to direct tissue analysis of small organic molecules. In this manuscript, we demonstrate the use of on-tissue chemical derivatization of a small organic molecule, 3-methoxysalicylamine (3-MoSA) a scavenger of γ -ketoaldehydes. Derivatization of 3-MoSA with 1,1′-thiocarbonyldiimidazole (TCDI) results in an oxothiazolidine derivative which is detected with much greater sensitivity by MALDI than 3-MoSA itself. TCDI treatment of tissue from mice dosed with 3-MoSA allowed images to be obtained showing its spatial distribution as well as its pharmacokinetic profile in different organs. These images correlated well with results obtained from HPLC-MS/MS analyses of the same tissues. These results provide proof-of-concept that on-tissue chemical derivatization can be used to improve detection of a small organic molecule by MALDI-IMS.

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

“…The overall sensitivity of MALDI-MSI can be enhanced to some extent by optimizing the type of matrix used, the matrix solvent composition [20], the method of matrix application [21], and the tissue clean up protocol [22], or by chemical derivatization [23][24][25][26][27].…”

Probe-based chemical modulations of tissues for IMS

“…When filtering the ions using collision-induced dissociation, the analyte is fragmented and imaging is based on the major transitions of the product ions [31][32][33][34]. An alternative approach to avoid matrix interference in the analysis of small molecules involves using high resolution/ high mass accuracy instrumentation.…”

Small molecule-sensing strategy and techniques for understanding the functionality of green tea

“…5) To overcome the limitation of the 1,5-DAN-MALDI-MSI technique and to ensure its practical use, further improvement of its detection sensitivity, such as employing a targeted selective reaction monitoring mode (SRM) approach using a triple quadrupole system (QqQ), 89) application of a Fourier transform ion cyclotron resonance-MS (FT-ICR-MS) instrument capable of accumulating continuously selected ions, 90) and on-tissue chemical derivatization approaches to increase the ionization efficiency 91,92) as well as the improvement of MALDI efficiency based on matrix choice and development, may be required. Additionally, other studies including kinetic histochemistry, 80,84,93) microscopic analysis with high-spatial resolution, [94][95][96] 3D imaging, [97][98][99] , and distribution of other metabolites 86,99) will be required to unravel both the biological consequences of biotransformation of the dietary polyphenol and its mechanism (s) of action.…”