title: High-performance liquid chromatographic method for mycophenolic acid and its glucuronide in serum and urine.
abstract: OBJECTIVE
  To develop a simple analytical method for monitoring serum and urine concentrations of mycophenolic acid (MPA), an active metabolic constituent of the immunosuppressive pro-drug mycophenolate mofetil, and its glucuronide.
  
  
  METHODS
  Serum samples were prepared by solid-phase extraction (SPE), while urine samples were simply diluted with water. Serum was added to an SPE cartridge, then washed twice with 5% methanol solution. The analytes were eluted with methanol containing benzoic acid as internal standard for mycophenolic acid glucuronide (MPAG). The resultant eluate was directly injected into a high-performance liquid chromatograph (HPLC) to determine MPAG. For the assay of MPA, the remaining eluate was dried under nitrogen and resolved in a mixture of acetonitrile and 20 mM phosphate buffer (pH 3.0).
  
  
  RESULTS
  The present methods were reproducible and accurate based on the intra- and inter-assay, and had detection limits of 0.225 microg/mL for MPA and 9.0 microg/mL for MPAG. The present methods enabled us to monitor the time course of changes in the concentrations of MPA and MPAG in serum and urine in a patient with a renal transplant during 12 h after ingestion of mycophenolate mofetil.
  
  
  CONCLUSIONS
  The HPLC method described should be useful for the routine monitoring of serum and urine concentrations of MPA and MPAG during immunosuppressive medication for renal transplantation.
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Maidashi, Fukuoka, Japan. dteshima@st.hosp.kyushu-u.ac.jp
authors.forename: D
authors.initials: D
authors.lastname: Teshima
authors.forename: K
authors.initials: K
authors.lastname: Otsubo
authors.forename: N
authors.initials: N
authors.lastname: Kitagawa
authors.forename: S
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Itoh
authors.forename: R
authors.initials: R
authors.lastname: Oishi
mesh_terms: D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring; D005965:Glucuronates / Q000097:blood / Q000652:urine; D020719:Glucuronides; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000652:urine*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D011355:Prodrugs / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D005965:Glucuronates; D020719:Glucuronides; D007166:Immunosuppressive Agents; D011355:Prodrugs; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid