期刊
BIOMEDICAL CHROMATOGRAPHY
卷 24, 期 10, 页码 1130-1135出版社
WILEY
DOI: 10.1002/bmc.1416
关键词
HPLC-ESI-MS/MS; HPLC-NMR; ilaprazole; metabolites; human urine
类别
资金
- National Scientific Foundation of China [30801421]
- Huge Project to Boost Chinese Drug Development [2009ZX09501-032]
- State Key Laboratory of Drug Research [SIMM0812KF-01]
- Doctoral Program of Higher Education of China [20070533002]
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 H-1-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. Copyright (C) 2010 John Wiley & Sons, Ltd.
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