HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (78) Citing Articles via Google Scholar Google Scholar Articles by Shipkova, M. Articles by Wieland, E. Search for Related Content PubMed PubMed Citation Articles by Shipkova, M. Articles by Wieland, E. Related Collections Drug Monitoring and Toxicology

Determination of the Acyl Glucuronide Metabolite of Mycophenolic Acid in Human Plasma by HPLC and Emit

^a Author for correspondence. Fax 49-551-398551; e-mail ewieland{at}med.uni-goettingen.de

Background: The acyl glucuronide (AcMPAG) of mycophenolic acid (MPA) has been found to possess pharmacologic and potentially proinflammatory activity in vitro. To establish its pharmacologic and toxicologic relevance in vivo, a reversed-phase HPLC method was modified to simultaneously determine MPA, the phenolic MPA-glucuronide (7-O-MPAG), and AcMPAG. In addition, cross-reactivity of AcMPAG in the Emit assay for MPA was investigated.

Methods: The procedure used simple sample preparation, separation with a Zorbax Eclipse-XDB-C8 column, and gradient elution. AcMPAG was quantified as 7-O-MPAG-equivalents.

Results: The assay was linear up to 50 mg/L for MPA, 250 mg/L for 7-O-MPAG, and 10 mg/L for AcMPAG (r >0.999). Detection limits were 0.01, 0.03, and 0.04 mg/L for MPA, 7-O-MPAG, and AcMPAG, respectively. The recoveries were 99–103% for MPA, 95–103% for 7-O-MPAG, and 104–107% for AcMPAG. The within-day imprecision was <5.0% for MPA (0.2–25 mg/L), <4.4% for 7-O-MPAG (10–250 mg/L), and 14% for AcMPAG (0.1–5 mg/L). The between-day imprecision was <6.2%, <4.5%, and 14% for MPA, 7-O-MPAG, and AcMPAG, respectively. When isolated from microsomes, purified AcMPAG (1–10 mg/L) revealed a concentration-dependent cross-reactivity in an Emit assay for the determination of MPA ranging from 135% to 185%. This is in accordance with the bias between HPLC and Emit calculated in 270 samples from kidney transplant recipients receiving mycophenolate mofetil therapy, which was greater (median, 151.2%) than the respective AcMPAG concentrations determined by HPLC. AcMPAG was found to undergo hydrolysis when samples were stored up to 24 h at room temperature or up to 30 days at 4 °C or -20 °C. Acidified samples (pH 2.5) were stable up to 30 days at -20 °C.

Conclusions: The HPLC and Emit methods for AcMPAG described here may allow investigation of its relevance for the immunosuppression and side effects associated with mycophenolate mofetil therapy.

The following articles in journals at HighWire Press have cited this article:

				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]

				O. J. Naderer, R. E. Dupuis, E. L. Heinzen, K. Wiwattanawongsa, M. W. Johnson, and P. C. Smith The Influence of Norfloxacin and Metronidazole on the Disposition of Mycophenolate Mofetil J. Clin. Pharmacol., February 1, 2005; 45(2): 219 - 226. [Abstract] [Full Text] [PDF]

				N. Picard, D. Ratanasavanh, A. Premaud, Y. Le Meur, and P. Marquet IDENTIFICATION OF THE UDP-GLUCURONOSYLTRANSFERASE ISOFORMS INVOLVED IN MYCOPHENOLIC ACID PHASE II METABOLISM Drug Metab. Dispos., January 1, 2005; 33(1): 139 - 146. [Abstract] [Full Text] [PDF]

				N. Picard and P. Marquet IN VITRO STUDY OF MYCOPHENOLIC ACID GLUCURONIDATION Drug Metab. Dispos., December 1, 2004; 32(12): 1524 - 1524. [Full Text] [PDF]

				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]

				G. Skopp, L. Potsch, R. Mattern, and R. Aderjan Short-Term Stability of Lysergic Acid Diethylamide (LSD), N-Desmethyl-LSD, and 2-Oxo-3-hydroxy-LSD in Urine, Assessed by Liquid Chromatography-Tandem Mass Spectrometry Clin. Chem., September 1, 2002; 48(9): 1615 - 1618. [Full Text] [PDF]

				B. Maes, M. Oellerich, J. L. Ceuppens, V. W. Armstrong, P. Evenepoel, D. Kuypers, T. Messiaen, M. Shipkova, E. Wieland, and Y. Vanrenterghem A new acute inflammatory syndrome related to the introduction of mycophenolate mofetil in patients with Wegener's granulomatosis Nephrol. Dial. Transplant., May 1, 2002; 17(5): 923 - 926. [Abstract] [Full Text] [PDF]

				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]

				G. Skopp and L. Potsch Stability of 11-Nor-{Delta}9-carboxy-tetrahydrocannabinol Glucuronide in Plasma and Urine Assessed by Liquid Chromatography-Tandem Mass Spectrometry Clin. Chem., February 1, 2002; 48(2): 301 - 306. [Abstract] [Full Text] [PDF]

				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]