title: The pharmacokinetics and tissue distribution of coumaroylspinosin in rat: A novel flavone C-glycoside derived from Zizyphi Spinosi Semen.
abstract: Zizyphi Spinosi Semen (ZSS) has a long history of sedative-hypnotic use in China. As a novel flavone C-glycoside, coumaroylspinosin is a main flavonoid only found in ZSS. Up to now, its pharmacokinetic information and tissue distribution in vivo are not available yet. With a simple, rapid and sensitive HPLC-MS/MS method, the pharmacokinetics and tissue distribution of coumaroylspinosin were investigated in Sprague-Dawley (SD) rats after its intravenous administration. Puerarin was used as the internal standard (IS). The samples were extracted by a simple protein precipitation method with methanol. The MS analysis was performed with multiple reaction monitoring (MRM), and the transitions were set at m/z 753.3→427.0 for coumaroylspinosin and m/z 415.3→295.3 for IS, respectively. The method was successfully applied for investigating the pharmacokinetics and tissue distribution of coumaroylspinosin in Sprague Dawley (SD) rats after tail vein injection with 4.0mg/kg of the flavonoid. The calibration curves covered over the range of 0.02-10μg/mL in plasma and various tissues samples with good linearity(r≥0.9956). The lower limit of quantification (LLOQ) in all samples was less than 20ng/mL. The intra- and inter-day precisions were below 15% and accuracy was from -3.78% to 4.68%. No significant matrix effect was observed, and the average extraction recovery was acceptable. Coumaroylspinosin could be cleared quickly from the rat plasma with the half-life (t1/2) of 1.86±0.15h. It was distribute widely in vivo, and the main tissue depots of coumaroylspinosin in rats were found to be intestine, muscle and lung. With the method, the pharmacokinetic parameters and tissue distribution of coumaroylspinosin in SD rats were investigated for the first time. The results demonstrated that coumaroylspinosin was distributed widely and rapidly in various rat tissues after intravenous administration.
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China; Tianjin Key Laboratory of Food Biotechnology, Tianjin 300134, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Wen
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China; Tianjin Key Laboratory of Food Biotechnology, Tianjin 300134, China. Electronic address: yqzhang2002@163.com.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin 300134, China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Yu
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
authors.forename: Bingcheng
authors.initials: B
authors.lastname: Pan
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
authors.affiliation: College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China; Tianjin Key Laboratory of Food Biotechnology, Tianjin 300134, China. Electronic address: xjbo@tjcu.edu.cn.
authors.forename: Junbo
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000032:analysis* / Q000378:metabolism*; D006027:Glycosides; D016014:Linear Models; D008297:Male; D009005:Monosaccharides / Q000032:analysis* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution; D031957:Ziziphus / Q000737:chemistry
chemical_list: C438934:C-glycoside; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D006027:Glycosides; D009005:Monosaccharides
keywords: Coumaroylspinosin; HPLC–MS/MS; Pharmacokinetics; Tissue distribution; Zizyphi Spinosi Semen