title: Simultaneous determination of mycophenolic acid and its metabolites by HPLC and pharmacokinetic studies in rat plasma and bile.
abstract: In this study, we determined the pharmacokinetics of mycophenolic acid (MPA) and its metabolites mycophenolic acid glucuronide (MPAG) and acyl glucuronide (AcMPAG) in rat plasma and bile, using a newly developed HPLC method. Protein precipitation and liquid-liquid extraction were employed in sample preparation of plasma and bile, respectively. The HPLC methods included a gradient elution consisting of acetonitrile and phosphate buffer at a flow rate of 1.2 mL/min, with UV detection at 254 nm. The HPLC method was found to be sensitive and linear (r(2) ≥ 0.9991, 1.0-128.0 and 0.25-32.0 mg/L for MPA; 1.0-128.0 and 0.5-64.0 mg/L for MPAG; 0.25-32.0 and 1.0-128.0 mg/L for AcMPAG in rat plasma and bile, respectively), precise (both the intra- and inter-day variability were ≤ 6.8%), and accurate (both the intra- and inter-day accuracy were between 92.2% and 105.4%). The average extraction efficiencies for MPA, MPAG and AcMPAG were 85.3%, 100.1%, and 94.7% in plasma, and 88.0%, 67.3%, and 68.3% in bile, respectively. The method was successfully employed for pharmacokinetic studies in plasma and bile after oral administration of mycophenolate mofetil (prodrug of MPA) in rats.
authors.affiliation: Department of Pharmacy, First People's Hospital Affiliated to Shanghai Jiao Tong University, China.
authors.forename: Jun-wei
authors.initials: JW
authors.lastname: Gao
authors.forename: Zhi-hai
authors.initials: ZH
authors.lastname: Peng
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Yan-kun
authors.initials: YK
authors.lastname: Guo
authors.forename: Gao-lin
authors.initials: GL
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020719:Glucuronides / Q000493:pharmacokinetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011355:Prodrugs; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020719:Glucuronides; D007166:Immunosuppressive Agents; D011355:Prodrugs; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid