1 hydroxymidazolam

EAM-2201 was obtained from Cayman Chemical Company (Ann Arbor, MI, USA). Acetaminophen, N-acetylserotonin, alamethicin, chenodeoxycholic acid, coumarin, diclofenac, dimethyl sulfoxide (DMSO), 7-hydroxycoumarin, midazolam, mycophenolic acid, naloxone, naloxone 3-β-d-glucuronide, NADPH, phenacetin, trifluoperazine, Trizma base and uridine 5′-diphosphoglucuronic acid (UDPGA) were purchased from Sigma-Aldrich (St. Louis, MO, USA). ¹³C₂,¹⁵N-Acetaminophen, bufuralol, N-desethylamodiaquine, 1′-hydroxybufuralol, d₉-1-hydroxybufuralol, 4-hydroxydiclofenac, 4-hydroxymephenytoin, 1′-hydroxymidazolam, [S]-mephenytoin and ultrapooled human liver microsomes (150 donors) were purchased from Corning Life Sciences (Woburn, MA, USA). N-Acetylserotonin β-d-glucuronide, chenodeoxycholic acid 24-acyl-β-glucuronide, mycophenolic acid β-d-glucuronide and SN-38 glucuronide were obtained from Toronto Research Chemicals (Toronto, ON, Canada). SN-38 was obtained from Santa Cruz Biotechnology (Dallas, TX, USA). Acetonitrile, methanol and water were of liquid chromatography–mass spectrometry (LC-MS) grade and purchased from Fisher Scientific Co. (Fair Lawn, NJ, USA). All other chemicals were of the highest quality available.

Epimagnolin A, eudesmin, fargesin, and magnolin were obtained from PhytoLab GmbH & Co. (Vestenbergsgreuth, Germany). Dimethyllirioresinol was a gift from Natural Medicine Research Center in Korea Research Institute of Biology and Biotechnology (Ochang, Korea). Bufuralol hydrochloride, 1′-hydroxybufuralol maleate, d₉-1′-hydroxybufuralol maleate, bupropion, hydroxybupropion, 4′-hydroxydiclofenac, 1′-hydroxymidazolam, 4′-hydroxymephenytoin, [S]-mephenytoin, and pooled human liver microsomes (catalog number 452161) were purchased from Corning Life Sciences (Woburn, MA, USA). Amodiaquine hydrochloride, N-desethylamodiaquine dihydrochloride, acetaminophen, coumarin, 7-hydroxycoumarin, diclofenac sodium, midazolam, phenacetin, and NADPH were obtained from Sigma-Aldrich (St. Louis, MO, USA). ¹³C₂, ¹⁵N-acetaminophen was obtained from Toronto Research Chemicals (Toronto, ON, Canada). Methanol, acetonitrile, and water (liquid chromatography-mass spectrometry [LC-MS] grade) were purchased from Fischer Scientific (Fair Lawn, NJ, USA). All other chemicals were of the highest quality available.

The following reagents were purchased from the listed sources: phenacetin (Nacalai Tesque, Kyoto, Japan); 4-acetamidophenol, (S)-warfarin, and 7-ethoxycoumarin (Sigma-Aldrich, MO, USA); (S)-7-hydroxywarfarin (BD Gentest, Woburn, MA, USA); midazolam and flunitrazepam (Wako Pure Chemical Industries, Osaka, Japan); 1′-hydroxymidazolam (Corning Incorporated, Steuben County, NY, USA); 4-acetoamidophenol-d4 (Cayman Chemical, Ann Arbor, MI, USA); oxidised β-nicotinamide-adenine dinucleotide phosphate oxidised form (NADP⁺), glucose-6-phosphate (G-6-P), glucose-6-phosphate dehydrogenase (G-6-PDH), β-nicotinamide-adenine dinucleotide reduced form (NADH), and β-nicotinamide-adenine dinucleotide phosphate reduced form (NADPH) (Oriental Yeast, Tokyo, Japan); polyclonal anti-human CYP1A2 antibody, polyclonal anti-human CYP2C9 antibody, and polyclonal anti-human CYP3A4 antibody (Nosan Corporation); polyclonal anti-calnexin antibody (Enzo Life Sciences); anti-cytochrome P450 reductase antibody (ab13513) and anti-cytochrome b₅ antibody (ab69801) (Abcam, CB, UK); horseradish peroxidase (HRP)-conjugated goat anti-rabbit IgG (DakoCytomation, Glostrup, Denmark); dimanganese decacarbonyl (DMDC) (Sigma-Aldrich, Steinheim, Germany); sodium cyanide and cytochrome c from horse heart (Nacalai Tesque, Kyoto, Japan). All other chemicals and reagents were of the highest commercially available quality.