title: LC-MS/MS determination and pharmacokinetic study of seven flavonoids in rat plasma after oral administration of Cirsium japonicum DC. extract.
abstract: BACKGROUND
  Cirsium japonicum DC., a Traditional Chinese Medicine, has the curative effect of antihemorrhagic and antitumor. Pharmacological studies prove that the curative effect may relate to the flavonoids. A simple and rapid resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was first developed and validated for the quantification of seven flavonoids including pectolinarin, linarin, pectolinarigenin, hispidulin, diosmetin, acacetin and apigenin in rat plasma after oral administration of Cirsium japonicum DC. extract.
  
  
  METHODS
  The chromatographic separation was achieved on a C18 column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and methanol as the mobile phase at a flow rate of 0.8mL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM) via an electrospray ionization (ESI) source in positive and negative ionization mode simultaneously. Samples were pre-treated by a single-step protein precipitation with methanol, and sulfamethoxazole was used as internal standard (IS).
  
  
  RESULTS
  The optimized mass transition ion-pairs (m/z) for quantization were 623.4/315.2 for pectolinarin, 593.3/285.1 for linarin, 315.3/300.2 for pectolinarigenin, 301.2/286.2 for hispidulin, 301.2/258.2 for diosmetin, 283.0/267.9 for acacetin, 269.0/117.0 for apigenin and 252.2/155.8 for IS. After oral administration of 6mL/kg Cirsium japonicum DC. extract in rats, the maximum plasma concentration (Cmax) of pectolinarin, linarin, pectolinarigenin, hispidulin, diosmetin, acacetin and apigenin were 876.77±97.34ng/mL, 86.79±1.70ng/mL, 6.13±0.12ng/mL, 32.85±2.50ng/mL, 37.2±2.04ng/mL, 19.02±1.29ng/mL and 148.26±20.63ng/mL, respectively. The time to reach the maximum plasma concentration (Tmax) was 5min for pectolinarin, linarin, pectolinarigenin, hispidulin, diosmetin, acacetin and 360min for apigenin. The intra-day and inter-day precisions (RSD%) for seven compounds were less than 13.16% and 7.77% and the accuracy (RE%) range from -7.92% to 14.77%.
  
  
  CONCLUSIONS
  This is the first research on the pharmacokinetic study of bioactive components in rat plasma after oral administration of Cirsium japonicum DC. extract. The results provided a meaningful basis for better understanding the absorption mechanism of Cirsium japonicum DC. and evaluating the clinical application of this herb medicine.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Qiaoyue
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, PR China. Electronic address: zhanglantong@263.net.
authors.forename: Lantong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D031180:Cirsium / Q000737:chemistry*; D005419:Flavonoids / Q000302:isolation & purification / Q000493:pharmacokinetics*; D008297:Male; D008516:Medicine, Chinese Traditional; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005419:Flavonoids; D010936:Plant Extracts
keywords: Cirsium japonicum DC; Flavonoids; HPLC–MS/MS; Pharmacokinetics