Stability of mycophenolic acid and glucuronide metabolites in human plasma and the impact of deproteinization methodology

Loor, Henriëtte de; Naesens, Maarten; Verbeke, Kristin; Vanrenterghem, Yves

doi:10.1016/j.cca.2007.11.033

Cited by 28 publications

(25 citation statements)

References 22 publications

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“…The issue of crossreactivity with AcMPAG was identified to overestimate total MPA levels; however, since the cross-reactivity level was <5%, it was felt that it would be inconsequential from a clinical perspective (Brandhorst et al, 2008). However, the authors pointed out a significant issue related to the hydrolysis of AcMPAG during storage and stressed the need for the stabilization of AcMPAG to prevent such hydrolysis (de Loor et al, 2008;Shipkova et al, 2000).…”

Section: Measurement Of Mpa In Vitreous Humormentioning

confidence: 93%

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

Syed

Srinivas²

2016

Biomedical Chromatography

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Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the analysis of MPA alone or with MPAG/AcMPAG in various biological specimens including plasma/serum, urine, ultrafiltrate, saliva, PBMC, dried blood spots, tissue extract, tumor biopsies and vitreous humor. Based on the need for experimental work, a proper choice of the assay and internal standard may be made using the choices in the literature. While the chemical methods involving high-performance liquid chromatography (HPLC) or LC coupled with triple quadrupole mass spectrometry (LC-MS/MS) are popular, enzymatic assays, in spite of their higher bias, have been used for the routine drug monitoring of MPA. The objectives of the present review are: (a) to provide a focused systematic compilation of the HPLC or LC-MS/MS methods for MPA, MPAG and/or AcMPAG published in the last decade (2005 to current) to enable visual comparison of the methods; (b) to compare and contrast a few enzymatic assays with those of the chemical methods; and (c) to discuss relevant issues/limitations and perspectives on select assays under various subheadings.

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Section: Measurement Of Mpa In Vitreous Humormentioning

confidence: 93%

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

Syed

Srinivas²

2016

Biomedical Chromatography

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“…The acyl glucuronide is unstable at neutral or alkaline pH, with a loss of approximately 25% after 12 hours and approximately 40% after 24 hours at room temperature (119). There are protocols that can be used to overcome the preanalytical problem (119)(120)(121)(122).…”

Section: Analytical Methods To Measure Mpa Concentrationsmentioning

confidence: 99%

Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation

Kuypers¹,

Meur²,

Cantarovich³

et al. 2010

Clinical Journal of the American Society of Nephrology

278

252

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“…Either a hydrolysis or an acyl migration can occur (de Loor et al, 2008;Horng et al, 2013;Shipkova et al, 2000;Trontelj et al, 2012). Hydrolysis leads to the regeneration of the pharmacologically active parent drug.…”

Section: Stability Of Mpa Mpag and Acmpag Under Various Collection Amentioning

confidence: 97%

Simultaneous quantification of mycophenolic acid and its glucuronide metabolites in human plasma by an UPLC–MS/MS assay

Zhang

Chow

Renbarger

2016

Biomedical Chromatography

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The aim of this study was to develop a reliable UPLC-MS/MS assay for accurate quantification of mycophenolic acid (MPA) and its glucuronide conjugates in human plasma. Plasma proteins were precipitated with acetonitrile and the chromatographic separation was achieved on a C18 column with a gradient elution. The detection was performed by a triple quadrupole mass spectrometer in the positive electrospray ionization and multiple reaction monitoring mode. Linearity of the assay was demonstrated over the range of 20-10,000 ng/mL for MPA and MPA glucuronide (MPAG), and 2-1000 ng/mL for acyl MPA glucuronide in human plasma. The assay was precise and accurate with coefficient of variation and bias <15%. MPA and MPAG were stable at 25 °C up to 1 day in both heparin- and EDTA-treated blood. In heparin- and EDTA-plasma, MPA and MPAG were stable for at least 1 week at 25 and 4 °C, and 1 month at -20 °C. However, 99% acyl MPA glucuronide degraded in both heparin- and EDTA-blood as well as plasma when stored at room temperature for 1 day. All the analytes remained stable for at least 3 months in acidified EDTA-plasma at -80 °C. The assay was successfully applied on patients post hematopoietic stem cell transplantation. Copyright © 2016 John Wiley & Sons, Ltd.

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Stability of mycophenolic acid and glucuronide metabolites in human plasma and the impact of deproteinization methodology

Cited by 28 publications

References 22 publications

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation

Simultaneous quantification of mycophenolic acid and its glucuronide metabolites in human plasma by an UPLC–MS/MS assay

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