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Drug Monitoring and Toxicology |
1
Abteilung Klinische Chemie, Georg-August-Universität Göttingen, D-37075 Göttingen, Germany.
2
Department of Pathology & Laboratory Medicine,
University of Pennsylvania Medical Center, Philadelphia, PA 19104.
a Address correspondence to this author at: Abteilung Klinische Chemie, Zentrum Innere Medizin, Georg-August-Universität, Robert Koch Strasse 40, D-37075 Göttingen, Germany. Fax 49-551-398551; e-mail ewieland{at}med.uni-goettingen.de.
We describe a reversed-phase HPLC method for determination of total mycophenolic acid (MPA), its free concentration (MPAf), and the glucuronide metabolite (MPAG), based on simple sample preparation and gradient elution chromatography. The compounds were quantified in parallel by absorbance at 254 nm and 215 nm in the internal standard mode. Linearity was verified up to 50 mg/L for MPA and up to 500 mg/L for MPAG (r >0.999). Detection limits at 215 and 254 nm were, respectively, 0.01 and 0.03 mg/L for MPA, and 0.03 and 0.1 mg/L for MPAG. The recovery of MPA was 95–106%;recovery of MPAG was 96–106%. The imprecision (CV) for MPA (0.2–25 mg/L) was <8.4% (254 nm) and <4.4% (215 nm) within day (n = 12) and <9.2% (254 nm) and <6.2% (215 nm) between days (n = 12). The imprecision for MPAG (10–250 mg/L) was <4.9% (254 nm) and <3.4% (215 nm) within day, and <6.1% (254 nm) and <5.9% (215 nm) between days. For quantification of MPAf, 100 µL of ultrafiltrate was applied directly to the column. The detection limit was 0.005 mg/L at 215 nm and 0.015 mg/L at 254 nm. In the range between 18–210 µg/L, the within-day CVs were <11.8% (n = 12) and the between-day CVs were <15.8% (n = 12).
The following articles in journals at HighWire Press have cited this article:
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  A. Jain, R. Venkataramanan, R. Sharma, T. Kwong, P. Abt, M. Orloff, R. Kashyap, G. Tsoulfas, and A. Bozorgzadeh Pharmacokinetics of Mycophenolic Acid in Live Donor Liver Transplant Patients vs Deceased Donor Liver Transplant Patients J. Clin. Pharmacol., May 1, 2008; 48(5): 547 - 552. [Abstract] [Full Text] [PDF]
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 G. Brandhorst, F. Streit, S. Goetze, M. Oellerich, and V. W. Armstrong Quantification by Liquid Chromatography Tandem Mass Spectrometry of Mycophenolic Acid and Its Phenol and Acyl Glucuronide Metabolites Clin. Chem., October 1, 2006; 52(10): 1962 - 1964. [Abstract] [Full Text] [PDF]
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X. Cussonneau, M. Bolon-Larger, and R. Boulieu Adsorption of Mycophenolic Acid and Its Phenolic Glucuronide to Glass, Polystyrene, and Polypropylene Containers. Clin. Chem., May 1, 2006; 52(5): 904 - 906. [Full Text] [PDF]
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 H. Tian, J. Ou, S. C. Strom, and R. Venkataramanan PHARMACOKINETICS OF TACROLIMUS AND MYCOPHENOLIC ACID ARE ALTERED, BUT RECOVER AT DIFFERENT TIMES DURING HEPATIC REGENERATION IN RATS Drug Metab. Dispos., March 1, 2005; 33(3): 329 - 335. [Abstract] [Full Text] [PDF]
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F. Streit, M. Shipkova, V. W. Armstrong, and M. Oellerich Validation of a Rapid and Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Free and Total Mycophenolic Acid Clin. Chem., January 1, 2004; 50(1): 152 - 159. [Abstract] [Full Text] [PDF]
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L. T. Weber, M. Shipkova, V. W. Armstrong, N. Wagner, E. Schutz, O. Mehls, L. B. Zimmerhackl, M. Oellerich, and B. Tonshoff Comparison of the Emit Immunoassay with HPLC for Therapeutic Drug Monitoring of Mycophenolic Acid in Pediatric Renal-Transplant Recipients on Mycophenolate Mofetil Therapy Clin. Chem., March 1, 2002; 48(3): 517 - 525. [Abstract] [Full Text] [PDF]
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 L. T. Weber, M. Shipkova, V. W. Armstrong, N. Wagner, E. Schuutz, O. Mehls, L. B. Zimmerhackl, M. Oellerich, and B. Tonshoff The Pharmacokinetic-Pharmacodynamic Relationship for Total and Free Mycophenolic Acid in Pediatric Renal Transplant Recipients: A Report of the German Study Group on Mycophenolate Mofetil Therapy J. Am. Soc. Nephrol., March 1, 2002; 13(3): 759 - 768. [Abstract] [Full Text] [PDF]
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M. Shipkova, V. W. Armstrong, M. G. Kiehl, P. D. Niedmann, E. Schutz, M. Oellerich, and E. Wieland Quantification of Mycophenolic Acid in Plasma Samples Collected during and Immediately after Intravenous Administration of Mycophenolate Mofetil Clin. Chem., August 1, 2001; 47(8): 1485 - 1488. [Full Text] [PDF]
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P. Morissette, M. Beaulieu, and B. Vinet A Specific Artificial Antibody toward Mycophenolic Acid Prepared by Molecular Imprinting Clin. Chem., September 1, 2000; 46(9): 1516 - 1518. [Full Text] [PDF]
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M. Shipkova, E. Schutz, V. W. Armstrong, P. D. Niedmann, M. Oellerich, and E. Wieland Determination of the Acyl Glucuronide Metabolite of Mycophenolic Acid in Human Plasma by HPLC and Emit Clin. Chem., March 1, 2000; 46(3): 365 - 372. [Abstract] [Full Text] [PDF]
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E. Schutz, M. Shipkova, V. W. Armstrong, E. Wieland, and M. Oellerich Identification of a Pharmacologically Active Metabolite of Mycophenolic Acid in Plasma of Transplant Recipients Treated with Mycophenolate Mofetil Clin. Chem., March 1, 1999; 45(3): 419 - 422. [Full Text] [PDF]
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M. Shipkova, V. W. Armstrong, T. Schneider, P. D. Niedmann, E. Schutz, E. Wieland, and M. Oellerich Stability of Mycophenolic Acid and Mycophenolic Acid Glucuronide in Human Plasma Clin. Chem., January 1, 1999; 45(1): 127 - 129. [Full Text] [PDF]
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