title: Gender-related pharmacokinetics and absolute bioavailability of diosbulbin B in rats determined by ultra-performance liquid chromatography-tandem mass spectrometry.
abstract: BACKGROUND
  Diosbulbin B (DB) is the main constituent of furano-norditerpenes in Dioscorea bulbifera Linn., which is widely distributed in China and was usually used as a remedy for sore throat, struma and tumor. Owing to its potential antitumor activity, DB has been considered as a promising candidate for drug development.
  
  
  OBJECTIVE
  To study the pharmacokinetic properties and excretion of DB in rats by a sensitive UPLC-MS/MS method. Absolute bioavailability and gender-related pharmacokinetic properties, as well as excretion fractions of DB in urine and feces after oral and intravenous administrations would be addressed for the first time.
  
  
  METHODS
  Sprague-Dawley rats were administrated orally (32mg/kg) and intravenously (0.5mg/kg) of DB, respectively. The concentrations of DB in rat plasma were determined by a sensitive and well-validated LC-MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration-time curve (AUC), elimination half time (t1/2), mean residence time (MRT), apparent volume of distribution (Vd) and clearance rate (CL) were estimated using a non-compartmental pharmacokinetics data analysis software. Urine and feces of rats were collected within 48h after oral administration (32mg/kg) and detected by UPLC-MS/MS and HPLC, respectively.
  
  
  RESULTS
  The standard curves of DB in rat plasma and urine showed good linearity in the concentration range of 1.0-515ng/mL in the method, with acceptable selectivity, precisions, recoveries, and stability. The oral absolute bioavailability of DB in female rats was 2.0%, significantly higher than that of males (0.3%) (p<0.05). Female rats demonstrated longer t1/2 and MRT (p<0.01), bigger Vd and higher CL (p<0.05) than males after intravenous administration of DB. Bigger but no significant difference in excretion fractions of urine and feces in female rats were observed, comparing to those in males.
  
  
  CONCLUSIONS
  A simple and sensitive UPLC-MS/MS method was developed to determine the pharmacokinetic profiles of DB in rats, as well as the excretion in rat urine. Gender exerted a significant influence on the pharmacokinetics and bioavailability of DB in rats. Female rats showed significantly better absorption of DB than males after oral administration.
authors: The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201210, China; The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201210, China.
authors: Baohua
authors: B
authors: Yang
authors: Xintang
authors: X
authors: Wang
authors: Wei
authors: W
authors: Liu
authors: Qian
authors: Q
authors: Zhang
authors: Kaixian
authors: K
authors: Chen
authors: Yueming
authors: Y
authors: Ma
authors: Changhong
authors: C
authors: Wang
authors: Zhengtao
authors: Z
authors: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D027742:Dioscorea / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012727:Sex Characteristics; D053719:Tandem Mass Spectrometry
chemical_list: D004365:Drugs, Chinese Herbal; D006576:Heterocyclic Compounds, 4 or More Rings; C569454:diosbulbin B
keywords: Absolute bioavailability; Diosbulbin B; Excretion; Gender difference; Pharmacokinetics; UPLC–MS/MS