Theophylline

The following compounds were purchased commercially from the sources indicated: allopurinol, benzbromarone, cyclosporine, D-fructose, elacridar, furosemide, hydrochlorothiazide, nicotinic acid, oxypurinol, rosuvastatin calcium salt, salicylic acid, 4-hydroxy chalcone (Wako Fine Chemical, Osaka, Japan); atorvastatin, chlorothiazide, febuxostat, mizoribine, pyrazinecarboxylic acid, ribavirin, tacrolimus, xylitol (Tokyo Chemical Industry, Tokyo, Japan); ethambutol, losartan (LKT Laboratories, St Paul, MN, USA); fenofibrate, probenecid, sulfasalazine, Ko143, ATP, AMP, creatine phosphate disodium salt tetrahydrate, creatine phosphokinase type I from rabbit muscle (Sigma-Aldrich, St. Louis, MO, USA); pyrazinamide (ACROS ORGANICS, Geel, Belgium); theophylline (Nacalai Tesque, Kyoto, Japan); and topiroxostat (MedChem Express, Princeton, NJ, USA). The [8-¹⁴C]-uric acid (53 mCi/mmol) was from American Radiolabeled Chemicals (St. Louis, MO, USA). All other chemicals used were commercially available and of analytical grade.

CO₂ (99.9%), used as the SFC mobile phase, was purchased from Iwatani Corporation (Osaka, Japan). LC grade ethanol, methanol, n-hexane, and formic acid were purchased from Nacalai Tesque (Kyoto, Japan). As test solutes, cinnamyl alcohol, benzene, toluene, p-xylene, benzyl alcohol, p-terphenyl, caffeine, and theophylline were purchased from Nacalai Tesque (Kyoto, Japan), and 4-nitrobenzyl alcohol, 4-hydroxymethylbenzoic acid, 4-aminobenzyl alcohol, 1,4-benzenedimethane, 4-tert-butylbenzyl alcohol, 1-naphthalenemethanol, 2-(benzyloxy) ethanol, o-terphenyl, m-terphenyl, 1,3,5-tri-tert-butylbenzene, and theobromine were purchased from Tokyo Chemical Industry Co. (Tokyo, Japan). Each solute was diluted with methanol to 0.1–20 g/L to yield similar peak areas.