title: Simultaneous determination of nine coumarins in rat plasma by HPLC-MS/MS for pharmacokinetics studies following oral administration of Fraxini Cortex extract.
abstract: A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination of nine coumarins including aesculin, aesculetin, fraxin, fraxetin, scopoletin, isoscopoletin, 6-hydroxy-7,8-dimethoxy coumarin, 8-hydroxy-6,7-dimethoxy coumarin and umbelliferone in rat plasma using nodakenin as the internal standard (IS). The plasma samples were pretreated by a one-step direct protein precipitation with methanol. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of methanol and water (containing 0.05% acetic acid). All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring (MRM) mode. This method was fully validated in terms of the sensitivity, specificity, accuracy, precision (intra- and inter-day), matrix effect, recovery as well as the stability of the analyte under various conditions, and the results satisfied the requirements of biological sample measurement. The validated method was successfully applied to pharmacokinetic study of the nine coumarins in rat plasma after oral administration of Fraxini Cortex aqueous extract, among which the pharmacokinetics of four coumarins including fraxetin, isoscopoletin, 6-hydroxy-7,8-dimethoxy coumarin and 8-hydroxy-6,7-dimethoxy coumarin were studied for the first time.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China; Jincheng General Hospital, General Hospital (Medical Group) of Shanxi Jincheng Anthracite Mining Group, Jincheng 048006, PR China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China; Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, PR China. Electronic address: qiaowang88@hotmail.com.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, the First Hospital of Shijiazhuang in Hebei, Shijiazhuang 050011, PR China. Electronic address: jshm2008@sina.com.
authors.forename: Shumin
authors.initials: S
authors.lastname: Jin
mesh_terms: D000284:Administration, Oral; D031319:Aesculus; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003374:Coumarins / Q000097:blood*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003374:Coumarins; D004365:Drugs, Chinese Herbal; C517354:horse chestnut seed
keywords: Coumarins; Fraxini cortex; HPLC–MS/MS; Pharmacokinetics study