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Titolo:
The apparent inhibition of inosine monophosphate dehydrogenase by mycophenolic acid glucuronide is attributable to the presence of trace quantities of mycophenolic acid
Autore:
Korecka, M; Nikolic, D; van Breemen, RB; Shaw, LM;
Indirizzi:
Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 pt Pathol, Philadelphia, PA 19104 USA Univ Penn, Med Ctr, Dept Lab Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 t Lab Med, Philadelphia, PA 19104 USA Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA Univ Illinois Chicago IL USA 60612 & Pharmacognosy, Chicago, IL 60612 USA
Titolo Testata:
CLINICAL CHEMISTRY
fascicolo: 7, volume: 45, anno: 1999,
pagine: 1047 - 1050
SICI:
0009-9147(199907)45:7<1047:TAIOIM>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
BINDING; PHARMACOKINETICS; METABOLISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
13
Recensione:
Indirizzi per estratti:
Indirizzo: Shaw, LM Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 , Philadelphia, PA 19104 USA
Citazione:
M. Korecka et al., "The apparent inhibition of inosine monophosphate dehydrogenase by mycophenolic acid glucuronide is attributable to the presence of trace quantities of mycophenolic acid", CLIN CHEM, 45(7), 1999, pp. 1047-1050

Abstract

Background: Mycophenolic acid glucuronide, the primary metabolite of the immunosuppressive agent mycophenolic acid, affords weak inhibition of proliferating and resting lymphocytes and recombinant human inosine monophosphatedehydrogenase in comparison to the active drug. We evaluated the hypothesis that mycophenolic acid is a trace contaminant of the glucuronide metabolite preparation and that this accounts for the observed effects of mycophenolic acid glucuronide on human inosine monophosphate dehydrogenase catalyticactivity both in lymphocytes and the pure enzyme. Methods: We used negative ion electrospray HPLC-mass spectrometry (HPLC-MS) and HPLC-tandem MS (HPLC-MS-MS) to identify mycophenolic acid as a contaminant of mycophenolic acid glucuronide. Quantification of the mycophenolic acid contaminant was achieved using a negative ion electrospray HPLC-MS method in the selected-ion monitoring mode. Results: Trace amounts of mycophenolic acid were detected and definitivelyidentified in the mycophenolic acid glucuronide preparation by the HPLC-MS-MS analysis. In addition to having identical HPLC retention times, pure mycophenolic acid and the contaminant produced the following major fragments upon HPLC-MS-MS analysis: deprotonated molecular ion, m/z 319; and fragmentions, mit 275, 243, 205, and 191 (the most abundant fragment ion). Using the negative ion electrospray HPLC-MS procedure in the selected-ion monitoring mode, the quantity of the contaminant mycophenolic acid was determined to be 0.312% +/- 0.0184% on a molar basis. Conclusion: These data provide strong support for the proposal that the apparent inhibition of the target enzyme inosine monophosphate dehydrogenase by mycophenolic acid glucuronide is attributable to the presence of trace amounts of contaminant mycophenolic acid. (C) 1999 American Association for Clinical Chemistry.

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Documento generato il 04/04/20 alle ore 21:47:31