title: Identification and analysis of gastrodin and its five metabolites using ultra fast liquid chromatography electrospray ionization tandem mass spectrometry to investigate influence of multiple-dose and food.
abstract: A reliable and highly sensitive ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) analytical method was developed for identification and quantification of gastrodin (GAS) and its metabolites in rat plasma. Five metabolites were identified: p-formylphenyl-β-d-glucopyranoside (M1), p-hydroxybenzonic acid (M2), p-hydroxybenzyl alcohol (M3), p-formaldehydephenyl-β-d-glucopyranoside (M4), p-hydroxybenzaldehyde (M5). The molecular structures of metabolites were proposed based on the characters of their precursor ions, product ions and chromatographic retention time. Four of them were reported firstly in rat plasma. This method involved the addition of bergeninum as the internal standard (IS), UFLC separation, and quantification by MS/MS system using negative electrospray ionization in the multiple reaction monitoring (MRM) mode. The lower limit of quantification of gastrodin and five metabolites were all 1ng/mL. The method was linear in the concentration range of 0.001-10μg/mL. The intra- and inter-day precisions (R.S.D %) were within 15.0% for all analytes. No interference was noted due to endogenous substances. All analytes were stable in rat plasma stored at room temperature and 4°C for at least 4h, -20°C combined with three freeze-thaw cycles for at least 1 month. By this method, the influence of multiple-dose and food on the pharmacokinetics behaviors of GAS and its metabolites were studied for the first time. We hope pharmacokinetic data of present study may inspire rational clinical usage of GAS.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24# Tongjia Xiang, Nanjing 210009, Jiangsu, China; Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24# Tongjia Xiang, Nanjing 210009, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China.
authors.forename: Haitang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Junsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24# Tongjia Xiang, Nanjing 210009, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24# Tongjia Xiang, Nanjing 210009, Jiangsu, China.
authors.forename: Kelvin D G
authors.initials: KD
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24# Tongjia Xiang, Nanjing 210009, Jiangsu, China.
authors.forename: Qingwang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24# Tongjia Xiang, Nanjing 210009, Jiangsu, China. Electronic address: cpu_lykong@126.com.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Kong
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000097:blood / Q000302:isolation & purification; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics; D002491:Central Nervous System Agents / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics; D062385:Hydroxybenzoates / Q000097:blood / Q000302:isolation & purification; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards
chemical_list: D001547:Benzaldehydes; D001592:Benzyl Alcohols; D002491:Central Nervous System Agents; D005960:Glucosides; D062385:Hydroxybenzoates; C018966:4-hydroxybenzyl alcohol; C045345:gastrodin; C011483:4-hydroxybenzaldehyde
keywords: Food; Gastrodin; Metabolites; Multiple-dose; Pharmacokinetics; UFLC-ESI–MS/MS