Carbazeran

Ketoprofen, zidovudine, dextromethorphan, dextrorphan, diclofenac, repaglinide, carbazeran, irinotecan, telmisartan, and quinidine were purchased from Sigma-Aldrich (St. Louis, MO, USA). Lorazepam, naloxone, 4′-hydroxydiclofenac, diclofenac-glucuronide, 3-hydroxyquinidine, 4-hydroxycarbazeran, naloxone-glucuronide, efavirenz, 7-hydroxyefavirenz, telmisartan-glucuronide, and posaconazole were purchased from Toronto Research Chemicals (Toronto, Canada). Cryopreserved hepatocyte recovery medium, William's E medium, primary hepatocyte plating supplements, primary hepatocyte maintenance supplements, and human hepatocytes (lot: Hu8264) were purchased from Thermo Fisher Scientific (Grand Island, NY, USA). Oxazepam, midazolam, and 1′-hydroxymidazolam were synthesized at F. Hoffmann-La Roche Ltd. (Basel, Switzerland). All CN Bio components (controller, docking station, and drivers) and consumables (LC-12 plates) were acquired from CN Bio Innovations (Cambridge, UK) (Fig. S1 †).

Uridine 59-diphosphoglucuronic acid trisodium salt (UDPGA), NADPH, alamethicin from Trichoderma viride, adenosine 3-phosphate 5-phosphosulfate, diclofenac sodium salt, midazolam hydrochloride, felodipine, S-(+)-mephenytoin, raloxifene hydrochloride, lovastatin, nisoldipine, nifedipine, methadone, quinidine, testosterone, benzydamine hydrochloride, cisapride, cyclosporin, terbutaline, sildenafil, verapamil, trazodone, atorvastatin, simvastatin, buspirone, rifabutin, saquinavir, terfenadine, zolpidem, repaglinide, indinavir, alprazolam, carbazeran, enalapril, ramipril , and dabigatran etexilate were purchased from Sigma-Aldrich (St. Louis, MO). NADPH-regenerating system containing NADP + , glucose-6phosphate, and glucose-6-phosphate dehydrogenase was purchased from Corning (Wiesbaden, Germany). Organic solvents were of LC-mass spectrometry (MS) or higher quality grade and were acquired from VWR International (Radnor, PA) or Fisher Scientific UK Ltd (Loughborough, UK). Purified water was obtained from Milli-Q Integral 5 Water Purification System (Merck KGaA, Darmstadt, Germany). Phosphate buffer, HQM Hepatocyte/Enterocyte Incubation Medium, and Co-Factor N for MetMax were purchased from In Vitro ADMET Laboratories (Columbia, MD).