title: Identification of ilaprazole metabolites in human urine by HPLC-ESI-MS/MS and HPLC-NMR experiments.
abstract: Ilaprazole is a new proton pump inhibitor designed for the treatment of gastric ulcers, and limited data is available on the metabolism of the drug. In this article, the structural elucidation of urinary metabolites of ilaprazole in human was described by HPLC-ESI-MS/MS and stopped-flow HPLC-NMR experiments. Urinary samples were precipitated by sodium carbonate solution, and then extracted by liquid-liquid extraction after adding ammonium acetate buffer solution. The enriched sample was separated using a C(18) reversed-phase column with the mobile phase composed of acetonitrile and 0.05 mol/L ammonium acetate buffer solution in a gradient solution, and then directly coupled to ESI-MS/MS detection in an on-line mode or (1)H-NMR (500 MHz) spectroscopic detection in a stopped-flow mode. As a result, four sulfide metabolites, ilaprazole sulfide (M1), 12-hydroxy-ilaprazole sulfide (M2), 11,12-dihydroxy-ilaprazole sulfide (M3) and ilaprazole sulfide A (M4), were identified by comparing their MS/MS and NMR data with those of the parent drug and available standard compounds. The main biotransformation reactions of ilaprazole were reduction and the aromatic hydroxylation of the parent drug and its relative metabolites. The result testified that HPLC-ESI-MS/MS and HPLC-NMR could be widely applied in detection and identification of novel metabolites.
authors.affiliation: Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Zhou
authors.forename: Shuyun
authors.initials: S
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Tan
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.forename: Haitang
authors.initials: H
authors.lastname: Hu
authors.forename: Jin
authors.initials: J
authors.lastname: Tan
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D053858:Metabolic Networks and Pathways; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013454:Sulfoxides / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D013454:Sulfoxides; C119615:ilaprazole