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.
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.
Marshall
Peter
P
BioMolecular Analysis, Computational and Structural Chemistry, GlaxoSmithKline, Gunnels Wood Road, Stevenage, UK. Peter.S.Marshall@gsk.com
Toteu-Djomte
Valerie
V
Bareille
Philippe
P
Perry
Hayley
H
Brown
Gillian
G
Baumert
Mark
M
Biggadike
Keith
K
D000293:Adolescent; D000328:Adult; D000818:Animals; D001274:Atmospheric Pressure; D005591:Chemical Fractionation; D004423:Ear; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D036103:Nanotechnology; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D012867:Skin / Q000187:drug effects*; D012869:Skin Absorption; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013499:Surface Properties; D055815:Young Adult
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid