title: A metabolic way to investigate related hurdles causing poor bioavailability in oral delivery of isoacteoside in rats employing ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry.
abstract: BACKGROUND
  Isoacteoside (ISAT), a phenylethanoid glycoside that acts as the principal bioactive component in traditional Chinese medicines, possesses broad pharmacological effects such as neuroprotective, antihypertensive and hepatoprotective activities. However, its pharmaceutical development has been severely limited due to the poor oral bioavailability. It is essential and significant to investigate related hurdles leading to the poor bioavailability of isoacteoside.
  
  
  METHODS
  Whole animal metabolism studies were conducted in rats, followed by metabolic mechanism including gastrointestinal stability, intestinal flora metabolism and intestinal enzyme metabolism employing the powerful method ultrahigh-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC/QTOF-MS/MS).
  
  
  RESULTS
  A simple, rapid and sensitive method has been developed which comprehensively revealed the underlying cause of poor bioavailability of ISAT in a metabolic manner. The prototype of ISAT and its combined metabolites have not been detected in plasma. Furthermore, the residual content of the parent compound in in vitro experiments was approximately 59%, 5% and barely none in intestinal bacteria, intestinal S9 and simulated intestinal juice at 6 h, respectively.
  
  
  CONCLUSIONS
  The present work has demonstrated that the factors causing the poor bioavailability of isoacteoside should be attributed to the metabolism. In general, the metabolism that resulted from intestinal flora and intestinal enzymes were predominant reasons giving rise to the poor bioavailability of ISAT, which also suggested that metabolites might be responsible for the excellent pharmacological effect of ISAT. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Cui
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.|Jiangsu Kanion Parmaceutical Co. Ltd, Lianyungang, 222001, China.
authors.forename: Yingni
authors.initials: Y
authors.lastname: Pan
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yan
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Qu
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jiangsu Kanion Parmaceutical Co. Ltd, Lianyungang, 222001, China.|State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, 222001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005243:Feces / Q000737:chemistry; D005960:Glucosides / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005960:Glucosides; D010636:Phenols; C064683:isoacteoside