Correlation of Skin Blanching and Percutaneous Absorption for Glucocorticoid Receptor Agonists by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and Liquid Extraction Surface Analysis with Nanoelectrospray Ionization Mass Spectrometry

• Published in: Analytical chemistry (Washington) Vol. 82; no. 18; pp. 7787 - 7794
• Main Authors: Marshall, Peter, Toteu-Djomte, Valerie, Bareille, Philippe, Perry, Hayley, Brown, Gillian, Baumert, Mark, Biggadike, Keith
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.09.2010
• Subjects: Adolescent; Adult; Analytical chemistry; Animals; Atmospheric Pressure; Chemical Fractionation; Chemistry; Correlation analysis; Ear; Exact sciences and technology; Glucocorticoids - metabolism; Glucocorticoids - pharmacology; Humans; Liquids; Male; Mass spectrometry; Middle Aged; Nanotechnology; Receptors, Glucocorticoid - agonists; Skin; Skin - drug effects; Skin Absorption; Spectrometric and optical methods; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface Properties; Young Adult; Human; Agonist; Ethanol; Liquid liquid extraction; Use; Surface ionization; Time; Matrix assisted laser desorption ionization; Surface analysis; In vitro; Electrospray; Chemical enrichment; Percutaneous route; Absorption; Imaging; Glucocorticoid receptor; Skin; Mass spectrometry
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/ac1017524

Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their topical anti-inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin penetration correlates to the degree of skin blanching obtained for the same three compounds in human volunteers.