title: Determination of the metabolic profile of gentianine after oral administration to rats by high performance liquid chromatography/electrospray ionization-trap mass spectrometry.
abstract: We investigated the metabolic fate of gentianine after oral administration to Wistar rats for the first time. Liquid chromatography/ion trap mass spectrometry detected four metabolites secogentianoxide, gentiandiol, gentianepoxide and gentianoxide in rat plasma together with the original compound gentianine. The structures of the metabolites were identified by comparing the retention times, as well as MS (mass) and MS/MS (tandem mass) spectra with those of authentic compounds, which were synthesized from gentianine or isolated from the urine. Three of the metabolites, secogentianoxide, gentianepoxide and gentianoxide, are novel compounds. The major in vivo metabolic processes associated with gentianine include N-oxide, epoxidation, dihydroxylation of double bond and hydrolysis of lactone. Gentianine together with the metabolites in plasma were quantified using gentianone as the internal standard. The mean C(max) of G0, G1, G2 and G3 are 425.76, 287.56, 188.45 and 85.05 ng/mL, respectively. The mean T(max) of G0, G1, G2 and G3 are 1.16, 3.87, 6.23 and 4.28 h, respectively. The mean T(1/2) of G0, G1, G2 and G3 are 5.23, 12.34, 7.78 and 5.64 h, respectively. A comprehensive metabolic pathway was proposed. The new metabolites may shed light on clinical efficacy of gentianine.
authors: National TCM Key Lab of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors: Xiuhong
authors: X
authors: Wu
authors: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; Harbin Children's Hospital, Youyi Road 57, Harbin, China.
authors: Shuhan
authors: S
authors: Tang
authors: Harbin Children's Hospital, Youyi Road 57, Harbin, China.
authors: Yan
authors: Y
authors: Jin
authors: National TCM Key Lab of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors: Shanshan
authors: S
authors: Wang
authors: National TCM Key Lab of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
authors: Xijun
authors: X
authors: Wang
authors: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors: Masao
authors: M
authors: Hattori
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Shaanxi 710061, China.
authors: Hailong
authors: H
authors: Zhang
authors: National TCM Key Lab of Serum Pharmacochemistry, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: wangzhigang0513@vip.163.com.
authors: Zhigang
authors: Z
authors: Wang
mesh_terms: D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; C060402:gentianine
keywords: Gentianine; LC–MS; Metabolite