Alprazolam

Phenacetin, acetaminophen, 2-acetamidophenol, coumarin, 7-hydroxy-comuarin (umbelliferone), flurbiprofen, dextromethorphan, dextrorphan, trazodone, thymol, bupropion, 6-hydroxy-bupropion, alprazolam, 1′-hydroxy-alprazolam, NADP⁺, isocitrate dehydrogenase, and DL-isocitrate were purchased from Sigma-Aldrich (St. Louis, MO, USA). Pronethalol was from Tocris (Minneapolis, MN, USA). Propofol was provided by Zeneca Pharmaceuticals (Wilmington, DE, USA). 4′-hydroxy-flurbiprofen, 2-fluoro-4-biphenyl-acetic acid, 4-hydroxy-propofol, chlorzoxazone, and 6-hydroxy-chlorzoxazone were purchased from Toronto Research Chemicals (Toronto, ON, Canada). S-Mephenytoin and 4-hydroxymephenytoin were purchased from Gentest (Corning, Corning, NY, USA). GW340416A, a chemical analogue of bupropion, was kindly provided by GlaxoSmithKline (Research Triangle Park, NC, USA). Omeprazole was purchased from BeanTown Chemical, Inc. (Hudson, NH, USA) and omeprazole sulfone was purchased from Cayman Chemical Company (Ann Arbor, MI, USA). Sodium hydroxide, potassium phosphate monobasic and potassium phosphate dibasic and EDTA were purchased from J.T. Baker (Center Valley, PA, USA). HPLC-grade acetonitrile and methanol were purchased from Thermo Fisher Scientific (Waltham, MA, USA). Ultra-pure water was obtained using a Milli-Q^® Q-POD Millipore System (EMD Millipore, Burlington, MA, USA).

Chloroquine, 7-hydroxymitragynine, midazolam, mitragynine, and mitragynine-d₃ were purchased from Cayman Chemical (Ann Arbor, MI, USA). The kratom alkaloids speciogynine, mitraciliatine, speciociliatine, paynantheine, and isopaynantheine were isolated and purified from Mitragyna speciosa as detailed previously [7 (link)]; all standards were >95% pure as measured by ultraperformance liquid chromatography (UPLC). Alprazolam and tert-butyl methyl ether (t-BME) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Human liver microsomes (HLMs; H0604, mixed biological sex, pool of 15, lot 1010191) and human intestinal microsomes (HIMs; H0610.I, mixed biological sex, pool of 10, lot 1610314) were purchased from XenoTech, LLC (Kansas City, KS, USA). Acetonitrile and methanol were purchased from Fisher Scientific (Fair Lawn, NJ, USA). Blank human plasma (K₂EDTA, mixed biological sex, pooled, lot HMN99236) and whole blood (K₂EDTA, mixed biological sex, pooled, lot HMN541526) were purchased from BioIVT (Westbury, NY, USA). All other chemicals and reagents were analytical grade.

Imipramine ampoules (from Polfa, Poland) were diluted with normal saline. Vigabatrin oral powder (Aventis, France) was prepared in normal saline. Diazepam (Roch, Switzerland), alprazolam (Sigma-Aldrich), and zolpidem (Sigma-Aldrich) were suspended in 1% Tween 80 in saline solution.