U, F)575.014a 575.016b495.056, 464.020, 419.MC22H25BrN2O8S10.8 (P, U, F)589.030a 589.031b464.013, 419.M17-C27H31BrN2O9S17.9 (U)639.103a 639.b418.(Continued on following web page)April 2013 Volume 57 Numberaac.asm.orgDeng et al.TABLE 1 (Continued)Metabolite M17-2 Chemical formula C27H31BrN2O9S Proposed chemical structure Rt (min)c 21.7 (U, F) m/z [M 639.101a 639.101b H] Fragment ion(s) 432.MC28H33BrN2O9S20.two (P, U, F)653.114a 653.b477.M19-C27H31BrN2O10S12.1 (U, F)655.096a 655.096b530.087, 323.M19-C27H31BrN2O10S13.0 (U)655.093a 655.096b530.085, 323.M20-C28H33BrN2O10S9.7 (P, U, F)669.108a 669.b544.M20-C28H33BrN2O10S11.0 (P, U, F)669.110a 669.b544.M20-C28H33BrN2O10S16.9 (U)669.110a 669.112bM20-C28H33BrN2O10S18.1 (U)669.109a 669.112bMC27H31BrN2O11S12.7 (U, F)671.089a 671.b495.MC28H33BrN2O11S11.two (P, U, F)685.(S)-TRIP site 105a 685.107b509.071, 464.011, 419.a bMeasured m/z values for protonated ions. Precise m/z values for protonated ions. c Rt, retention time; P, plasma; U, urine; F, feces.lites have been compared with these detected in human urine. The newly identified metabolites had been M3-1 and M6-2, which were eluted at 20.four and 19.six min, respectively. Their structures have been proposed as 1-methylindole N-demethylated arbidol and 4=-hydroxylarbidol, respectively. Based on the high collision energy mass spectra, the chemical structure of M6-2 was additional confirmed by comparison having a reference typical. Arbidol was thepredominate element excreted in feces, accounting for 32.four in the dose, and the key metabolite in feces was the sulfate conjugate of arbidol (M10), accounting for 3.0 from the dose. The other oxidative metabolites (M5, M6-1, and M8) represented 2 of your dose. (iii) Plasma. A total of 16 metabolites had been detected within the human plasma extracts, and M6-1 was the key drug-relatedaac.asm.orgAntimicrobial Agents and ChemotherapyBiotransformation of Arbidol in HumansFIG 1 Metabolic profiles of arbidol immediately after a single oral administration of 200-mg arbidol hydrochloride capsules. (A) Pooled plasma samples collected at 2 hpostdose. (B) Pooled urine samples collected at 0 to 24 h postdose. (C) Pooled feces samples collected at 24 to 96 h postdose. On the left are shown metabolite profiles by MS detection, and around the right are metabolite profiles by UV detection at 316 nmponent, followed by the unmetabolized arbidol. The other metabolites that presented at relatively high levels in human plasma had been M5 and M8.4-Bromo-3,5-dimethylphenylboronic acid Formula Metabolites M1, M3-2, and M7 had been observed in plasma as minor phase I metabolites.PMID:33452002 These oxidative metabolites could be further metabolized to form phase II conjugates (M9-2, M11-2, M14-1, M15, M16, M20-1, M20-2, andM22). The glucuronide conjugate (M18) along with the sulfate conjugate (M10) in the parent drug have been also detected in plasma. All of those conjugates have been detected as minor metabolites. Pharmacokinetics of arbidol and metabolites M5, M6-1, and M8. Table two presents the pharmacokinetic parameters determined by noncompartmental evaluation. The imply plasma concentration-FIG 2 Identified metabolic processes of arbidol in humans. The significant metabolic pathway was sulfoxidation. Specifics from the chemical structures are shown inTable 1.April 2013 Volume 57 Numberaac.asm.orgDeng et al.TABLE two Pharmacokinetic parameters of arbidol and its 3 key metabolites in plasma of 4 wholesome male subjects immediately after a single oral administration of 200 mg of arbidol hydrochlorideValue Parameter Tmax (h) Cmax (ng/ml) AUC0-t (ng ?h ?ml 1) AUC0- (ng ?h ?ml 1) t1/2 (h) CL/F (lit.
