Effect of 2-(4-aminophenylmethyl)-6-hydroxy-3, 4-dihydronaphthalen-1(2H)-one on all-trans and 13-cis-retinoic acid levels in plasma quantified by high perfomance liquid chromatography coupled to tandem mass spectrometry.
The effect of the titled tetralone as a retinoic acid metabolism blocking agent (RAMBA) in vivo in comparison with ketoconazole, a well known cytochrome P450 inhibitor, was studied. Development of a HPLC/MS/MS method for the quantification of retinoic acid levels extracted from rat plasma was used to demonstrate that ketoconazole and the tetralone (100 mg/kg) enhanced the endogenous plasma concentration of retinoic acid. Levels of retinoid were raised from a control value of 0.11 to 0.15 and 0.17 ng/mL after treatment with tetralone and ketoconazole respectively showing that the tetralone and ketoconazole lead to comparable effects, indicating an inhibitory activity of the tetralone on retinoic acid metabolism.
Angotti
Marc
M
Pharmaceutical and Medicinal Chemistry, Saarland University, Universität des Saarlandes, PO Box 15 11 50, D-66041 Saarbrücken, Germany. rwh@mx.uni-saarland.de
Hartmann
Rolf W
RW
Kirby
Andrew J
AJ
Simons
Claire
C
Nicholls
Paul J
PJ
Sewell
Robert D E
RD
Smith
H John
HJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015474:Isotretinoin / Q000097:blood* / Q000737:chemistry; D007654:Ketoconazole / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D044024:Tetralones / Q000378:metabolism / Q000494:pharmacology; D014212:Tretinoin / Q000097:blood* / Q000737:chemistry
C477687:2-(4-aminophenylmethyl)-6-hydroxy-3,4-dihydronaphthalen-1(2H)-one; D009281:Naphthalenes; D044024:Tetralones; D014212:Tretinoin; D015474:Isotretinoin; D007654:Ketoconazole