title: Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.
abstract: BACKGROUND
  The pharmacokinetics properties of dihydromyricetin (DHM) are still unknown.
  
  
  OBJECTIVE
  This study investigates the pharmacokinetic characteristics of DHM using a sensitive and reliable LC-MS/MS method.
  
  
  METHODS
  A rapid and sensitive LC-MS/MS method was developed for the determination of DHM in male Sprague-Dawley rat plasma. Twelve rats were equally randomized into two groups, including the intravenous group (2 mg/kg) and the oral group (20 mg/kg). Blood samples (250 μL) were collected at designated time points and analyzed using this method. The pharmacokinetic parameters were calculated using DAS 3.0 pharmacokinetic software.
  
  
  RESULTS
  The calibration curve was linear within the range of 0.5-200 ng/mL (r > 0.998) with the lower limit of quantification at 0.5 ng/mL. After the intravenous injection, DHM reached a maximum concentration of 165.67 ± 16.35 ng/mL, and t1/2was 2.05 ± 0.52 h. However, DHM was not readily absorbed and reached Cmax21.63 ± 3.62 ng/mL at approximately 2.67 h following the oral administration of DHM, and t1/2was 3.70 ± 0.99 h. The MRT for the intravenous group and the oral group were 2.62 ± 0.36 and 5.98 ± 0.58 h, respectively. The AUC(0-t)for the intravenous group and the oral group were 410.73 ± 78.12 and 164.97 ± 41.76 ng·L/mL, respectively, so the absolute bioavailability of DHM was 4.02% which was poor.
  
  
  CONCLUSIONS
  The results indicated that the bioavailability was poor. Further work needs to be conducted to investigate the reason for poor bioavailability and improve this situation.
authors.affiliation: a Department of Endocrinology , Seventh People's Hospital of Shanghai University of TCM , Shanghai , China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: b Gamaknife Center, No 411 Hospital of the Chinese People's Liberation Army , Shanghai , China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yin
authors.affiliation: c Department of CT , First Affiliated Hospital of Nanyang Medical College , Nanyang , Henan , China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Department of Endocrinology , Seventh People's Hospital of Shanghai University of TCM , Shanghai , China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002853:Chromatography, Liquid / Q000592:standards; D044948:Flavonols / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D044948:Flavonols; C472036:dihydromyricetin
keywords: Absorption; Ampelopsis grossedentata; bioavailability; flavonoid