In Situ Hydrogel Conditioning of Tissue Samples To Enhance the Drug’s Sensitivity in Ambient Mass Spectrometry Imaging

Abstract

Ion suppression from the tissue matrix has a severe effect on the mass spectrometry imaging (MSI) of drugs. This problem hinders further applications of MSI in preclinical drug research and development. In this study, an in situ hydrogel conditioning method was developed to enhance the sensitivity of air-flow-assisted desorption electrospray ionization (AFADESI)-MSI. Instead of the traditional washing or digestion treatment in solvent, this method used a solid phase hydrogel to "wash" tissue sections. It was demonstrated that this in situ hydrogel conditioning method improved the drug signal by as much as 2- to 25-fold in MSI, especially for hydrophobic compounds. Furthermore, the obvious dislocation of analytes was not observed. The evaluation of spatial resolution indicated that the amount of dislocation in tissue sections with the hydrogel process was less than the resolution of AFADESI-MSI. The underlying reasons for the MSI signal enhancement were initially investigated. The decreased signal intensities of choline, betaine, and carnitine and the increased intensities of the [M + H]/[M + Na] and [M + H]/[M + K] ratios for drugs in the mass spectra of pretreated tissues provided evidence that this method can reduce the levels of highly competitive quaternary ammonium and inorganic salts in the tissues. The preformation of a thin liquid film for droplet pickup would also raise the ionization efficiency of drugs. These results demonstrated that this in situ hydrogel conditioning method provides a rapid and feasible approach to improving the sensitivity of ambient MSI for drug mapping in tissues.

Novel approach to enhance sensitivity in surface‐assisted laser desorption/ionization mass spectrometry imaging using deposited organic‐inorganic hybrid matrices

“…The presence of salts in biological tissue samples is one factor affecting imaging MS. Washing samples with an aqueous solution has been suggested as a solution to this problem, but doing so can reduce the spatial resolution because of the migration of the substance to be measured . Method D described in this paper was useful for removing the influence of salts while maintaining high spatial resolution using the sublimation method.…”

The Space Dimension at the Micro Level: Mass Spectrometry Imaging of Drugs in Tissues

“…Finally, some pretreatment protocols have been developed to boost sensitivity although they can be risky, altering the tissue structure or causing delocalization of the analytes. On tissue, a derivatization approach has been applied to detect drugs that are non‐ionizable per se (Manier et al, 2011; Shariatgorji et al, 2014; Barré et al, 2016), while sample conditioning with hydrogel, buffers, or organic solvents can increase sensitivity in MALDI imaging of different drugs (Quiason & Shahidi‐Latham, 2015; Song et al, 2017).…”

Recent Advances of Ambient Mass Spectrometry Imaging and Its Applications in Lipid and Metabolite Analysis

“…This method has a picomolar sensitivity for targeted drug molecules by virtue of high transport efficiency with the assistance of airflow, extended length and area of sampling, and it was successfully applied to the imaging of large, whole-body sections [15][16][17]. AFADESI could improve the signal of lipids and drugs by 2~25-fold by washing the whole body tissue sections of mice with in situ hydrogel [18]. Varying the spray solvent is a convenient method to improve sensitivity.…”