All reference materials were obtained from Sigma Aldrich, St Louis, MO, Toronto Research Chemicals, North York Ontario CA, and Cerilliant, Round Rock, TX, except norfluoxetine stereoisomers which were synthesized in house(3 (link)). Concentrations of omeprazole, 5-hydroxyomeprazole, dextromethorphan, dextrorphan, dextrorphan-O-glucuronide, midazolam and caffeine in plasma and urine were analyzed using a Shimadzu Prominence UHPLC (Tokyo, Japan) coupled to an AB Sciex API3200 MS/MS (Framingham, MA) as described previously (3 (link), 22 (link)). Cortisol, cortisone, 6β-hydroxycortisol, 6β-hydroxycortisone, lovastatin and hydroxylovastatin acid were analyzed using an Agilent 1290 UHPLC (Santa Clara, CA) coupled to an AB Sciex API5500 MS/MS. Analytes were separated using a Thermo Hypersil Gold 100x2.1mm, 1.9µm column (West Palm Peach, FL) with a gradient elution from 90% water with 0.1% formic acid:10% acetonitrile (0.5 min), to 90% acetonitrile by 3.5 minutes, held until 5 min, then allowed to re-equilibrate to initial conditions until 7 minutes. The (R)- and (S)- enantiomers of fluoxetine and norfluoxetine were separated using an Astec Chirobiotic V 250x2.1mm, 5µm (St. Louis, MO) column and isocratic elution with 10% water and 90% methanol with 10mM ammonium formate. All analytes were detected using positive electrospray ionization except for dextrorphan-O-glucuronide, 6β-hydroxycortisol, 6β-hydroxycortisone and hydroxylovastatin acid, which were detected using negative electrospray ionization. All MRM transitions (m/z) were as previously described (22 (link)) except the following: 272→128 (dextromethorphan), 258→157 (dextrorphan), 432→256 (dextrorphan-O-glucuronide), 195→138 (caffeine), 363→121 (cortisol), 361→163 (cortisone), 423→347 (6β-hydroxycortisol), 421→345 (6β-hydroxycortisone), 427→325 (lovastatin) and 421→319 (hydroxylovastatin acid). The injection volume for all assays was 10µL. The lower limits of quantitation were less than 1nM for all analytes, except for caffeine (15nM). Inter-day percent coefficient of variation for all analytes at 1nM (30nM for caffeine) was less than 15%. All samples were protein precipitated with 1:2 sample:acetonitrile, except omeprazole and 5-hydroxyomeprazole (2:3:1 sample:acetonitrile:methanol), centrifuged twice at 3000g for 15min and the supernatant was used for analysis. The organic solvent contained 100nM of d3-omeprazole, d4-midazolam, d6-fluoxetine or simvastatin as internal standards. Cortisol, cortisone, 6β-hydroxycortisol and 6β-hydroxycortisone were extracted from the 6 hr plasma sample and the 0–12 hr urine sample from control day 3 and study day 14 using a previously described liquid-liquid extraction method (23 (link)) with the addition of a second extraction and using the internal standard of 100nM 16β-methylprednisolone.