Optimization of dropletProbe-Mass Spectrometry for Whole-Body Tissue Distribution Analysis of Drug-Like Molecules.

Journal of the American Society for Mass Spectrometry
Bingming ChenMark Cancilla

Abstract

dropletProbe mass spectrometry (MS) is an emerging tool for the rapid ex vivo analysis of drugs in tissues and whole-body sections. Its use has been demonstrated to better understand a drug's absorption, distribution, metabolism, and excretion (ADME) properties. To further optimize the overall utility of this technique, it is important to characterize and understand the various tissue matrix effects and extraction solvents on the overall performance of dropletProbe MS analyses. Herein, we systematically evaluated the impact of extraction solvents and various tissues on the relative detected signal intensities of a test set of diverse drugs. It was observed that the tissue matrix had a minimal effect on the performance of dropletProbe MS for the limited set of tested compounds once an optimized extraction solvent was identified. A general starting extraction solvent of 1:1 acetonitrile/water (v:v) was identified to efficiently extract the test set of compounds from various tissues. Next, the optimized conditions were used to map the distribution of the drug diclofenac and its metabolites in whole-body mouse sections. The relative tissue distribution of diclofenac and its metabolites, including the phase II acyl-glucuronide metab...Continue Reading

References

May 1, 1995·Pharmaceutical Research·R J SawchukH S Lau
Jul 23, 2003·Current Drug Metabolism·Wei Tang
Aug 26, 2010·Molecular & Cellular Proteomics : MCP·Pierre ChaurandRichard M Caprioli
May 28, 2014·Rapid Communications in Mass Spectrometry : RCM·Vilmos Kertesz, Gary J Van Berkel
Nov 22, 2014·Bioanalysis·Guillaume HochartJonathan Stauber
Mar 17, 2018·Analytical and Bioanalytical Chemistry·David BonnelKim T Nielsen

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