title: An integrated strategy based on UPLC-DAD-QTOF-MS for metabolism and pharmacokinetic studies of herbal medicines: Tibetan "Snow Lotus" herb (Saussurea laniceps), a case study.
abstract: BACKGROUND
  Saussurea laniceps Hand.-Mazz. (SL) has long been used under the herbal name Tibetan "Snow Lotus" for the treatment of rheumatoid arthritis, stomachache and dysmenorrhea in Tibetan folk medicine. Since herbal medicine (HM) is a synergistical system with multiple components, both of the metabolism and pharmacokinetic studies of HM are interdependent. This study aimed to develop an integrated strategy based on the UPLC-DAD-QTOF-MS technique for metabolism and pharmacokinetic studies of HM.
  
  
  METHODS
  SL was used here as a test herb to verify the feasibility of the proposed strategy. SL was administered to rats, then, the blood plasma, urine and feces were analyzed to determine the metabolic profiles. Using our strategy, umbelliferone and scopoletin were evaluated to be the key bioactive components. Their pharmacokinetic parameters were measured and biotransformation pathways were elucidated.
  
  
  RESULTS
  After oral administration of SL to rats, 17 components in blood, 10 components in urine and 2 components in feces were identified and characterized using our UPLC-DAD-QTOF-MS method. Umbelliferone, scopoletin and their metabolites were found to be the major components involved in the metabolism process. Literature reports also suggest that umbelliferone and scopoletin are responsible for the therapeutic effects of SL, thus these two components were selected as the active markers for pharmacokinetic study. In the test of validity, the established method presented good linearity with R(2)>0.99. The relative standard deviation value was below 13.9% for precision, and recovery studies for accuracy were found to be within the range 91.8-112.5%.
  
  
  CONCLUSIONS
  The present strategy offers, simultaneously, precision in quantitative analysis (metabolism study) and accuracy in quantitative analysis (pharmacokinetic study) with greater efficiency and less costs, which is therefore reliably used for integrated metabolism and pharmacokinetic studies of HM.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.affiliation: School of Biomedical Science, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Yi-Na
authors.initials: YN
authors.lastname: Tang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Zhi-Tao
authors.initials: ZT
authors.lastname: Liang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Zhao
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Bian
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Yang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Special Administrative Region, PR China. Electronic address: hbchen@hkbu.edu.hk.
authors.forename: Hu-Biao
authors.initials: HB
authors.lastname: Chen
mesh_terms: D000818:Animals; D019659:Asteraceae; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008519:Medicine, Traditional; D064209:Phytochemicals / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017207:Rats, Sprague-Dawley; D012603:Scopoletin / Q000097:blood / Q000493:pharmacokinetics; D014468:Umbelliferones / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D064209:Phytochemicals; D010936:Plant Extracts; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D012603:Scopoletin
keywords: Herbal medicine; Metabolism; Pharmacokinetics; Saussurea laniceps; Snow lotus; UPLC–DAD–QTOF-MS