Microsome biocolloids for rapid drug metabolism and inhibition assessment by LC-MS.
Rat liver microsomes attached to nanoparticles were used for LC-MS studies of CYP3A and 2E1 enzymes in metabolism of N-nitroso compounds. Using these biocolloids, turnover rates were measured within 2 min. Inhibitor IC(50) values for ketoconazole (KET) and 4-methylpyrazole (4-MEP) were estimated.
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060. USA.
Besnik
B
Bajrami
Sadagopan
S
Krishnan
James F
JF
Rusling
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D003102:Colloids / Q000737:chemistry; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000077604:Fomepizole; D020128:Inhibitory Concentration 50; D007654:Ketoconazole / Q000008:administration & dosage / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D053758:Nanoparticles; D009603:Nitroso Compounds / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods
D003102:Colloids; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D011720:Pyrazoles; D000077604:Fomepizole; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole