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High‐performance liquid chromatographic method for mycophenolic acid and its glucuronide in serum and urine
Author(s) -
Teshima D.,
Otsubo K.,
Kitagawa N.,
Yoshimura S.,
Itoh Y.,
Oishi R.
Publication year - 2003
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1046/j.1365-2710.2003.00450.x
Subject(s) - chromatography , mycophenolic acid , chemistry , urine , elution , high performance liquid chromatography , glucuronide , solid phase extraction , therapeutic drug monitoring , mycophenolate , analyte , pharmacokinetics , transplantation , pharmacology , medicine , biochemistry , surgery
Summary 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 m m phosphate buffer (pH 3ḃ0). Results: The present methods were reproducible and accurate based on the intra‐ and inter‐assay, and had detection limits of 0ḃ225 μg/mL for MPA and 9ḃ0 μg/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. Conclusion: 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.