title: In vivo metabolites and plasma exposure of TongMai Keli analyzed by UHPLC/DAD/qTOF-MS and LC/MS/MS.
abstract: BACKGROUND
  TongMai Keli (TM) is a widely used traditional Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular diseases. It is composed of Puerariae Lobatae Radix (roots of Pueraria lobata (Willd.) Ohwi), Salviae Miltiorrhizae Radix (roots of Salvia miltiorrhiza Bge.), and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort.). The aim of this study is to identify the in vivo metabolites of TM, and to elucidate the pharmacokinetics of TM constituents and their metabolites.
  
  
  METHODS
  For metabolites identification, TM was orally administered to rats (n=3), and the metabolites in plasma were identified by UHPLC/DAD/qTOF-MS analysis and β-glucuronidase hydrolysis. For pharmacokinetic study, rats (n=10) were treated with TM at a clinical dose, and the plasma was analyzed by LC/MS/MS.
  
  
  RESULTS
  A total of 25 metabolites from TM were identified in rats plasma. Glucuronide and sulfate conjugations were the major metabolic reactions, and produced 14 metabolites. The analytical method for pharmacokinetic study was fully validated with good linearity (r>0.99), wide dynamic ranges (6-6000 ng/mL), and low variations (<14.3%). The plasma concentration-time curves of puerarin and nine metabolites were profiled.
  
  
  CONCLUSIONS
  Isoflavones from Puerariae Lobatae Radix were the major metabolites in rat plasma after oral administration of TM. Puerarin and other isoflavone glycosides could reach their first C(max) within 30 min, and were then rapidly eliminated, followed by their phase II metabolites.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Chun-fang
authors.initials: CF
authors.lastname: Liu
authors.forename: Xue
authors.initials: X
authors.lastname: Qiao
authors.forename: Ke-di
authors.initials: KD
authors.lastname: Liu
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Miao
authors.forename: Yan-jiao
authors.initials: YJ
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Bo
authors.forename: Ren-bing
authors.initials: RB
authors.lastname: Shi
authors.forename: De-an
authors.initials: DA
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Ye
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D007529:Isoflavones / Q000097:blood; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D007529:Isoflavones; C581903:TongMai Keli