Mapping drug distribution in brain tissue using liquid extraction surface analysis mass spectrometry imaging

Analytical Chemistry
John G SwalesRichard J A Goodwin

Abstract

Liquid extraction surface analysis mass spectrometry (LESA-MS) is a surface sampling technique that incorporates liquid extraction from the surface of tissue sections with nanoelectrospray mass spectrometry. Traditional tissue analysis techniques usually require homogenization of the sample prior to analysis via high-performance liquid chromatography mass spectrometry (HPLC-MS), but an intrinsic weakness of this is a loss of all spatial information and the inability of the technique to distinguish between actual tissue penetration and response caused by residual blood contamination. LESA-MS, in contrast, has the ability to spatially resolve drug distributions and has historically been used to profile discrete spots on the surface of tissue sections. Here, we use the technique as a mass spectrometry imaging (MSI) tool, extracting points at 1 mm spatial resolution across tissue sections to build an image of xenobiotic and endogenous compound distribution to assess drug blood-brain barrier penetration into brain tissue. A selection of penetrant and "nonpenetrant" drugs were dosed to rats via oral and intravenous administration. Whole brains were snap-frozen at necropsy and were subsequently sectioned prior to analysis by matrix-as...Continue Reading

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Citations

Jun 27, 2017·Journal of Proteome Research·Marialaura DililloLiam A McDonnell
Dec 7, 2018·The Analyst·Fan PuZheng Ouyang
Aug 1, 2019·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Gregory R HammRichard J A Goodwin
Jan 1, 2019·Mass Spectrometry·Britt S R ClaesRon M A Heeren
Jul 28, 2020·SLAS Discovery·Richard J A GoodwinJosephine Bunch
Feb 6, 2020·Biochemical Society Transactions·Oliver J Hale, Helen J Cooper
Jun 24, 2016·Cancer Research·Zoe HallJulian L Griffin
Nov 23, 2017·Current Opinion in Chemical Biology·Rian L GriffithsHelen J Cooper
Jun 30, 2018·Current Opinion in Chemical Biology·Brendan PrideauxVéronique Dartois
Aug 29, 2018·Journal of the American Society for Mass Spectrometry·Andrea F Lopez-ClavijoHelen J Cooper
May 6, 2019·Analytical Chemistry·Jiaquan XuHuanwen Chen
Oct 24, 2018·Analytical Chemistry·Rian L GriffithsHelen J Cooper
Feb 21, 2019·ACS Medicinal Chemistry Letters·Robert W Johnson, Nari Talaty

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