Manual and automated (robotic) high-performance liquid chromatography methods for the determination of mycophenolic acid and its glucuronide conjugate in human plasma

Tsina, Irene; Chu, Fulong; Hama, Kumiko; Kaloostian, Martin; Tam, Y L; Tarnowski, Thomas; Wong, Belinda

doi:10.1016/0378-4347(95)00343-6

Cited by 110 publications

(3 citation statements)

References 5 publications

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“…Blood samples were collected in ethylenediaminetetraacetic acid tubes, and total MPA plasma concentrations were quantified by reverse-phase high performance liquid chromatography (HPLC) with UV detection (adapted from Tsina et al ). (7, 16, 17) The dynamic range was 0.2 to 30 μg/mL and the interday coefficient of variation was less than 10%. (7)…”

Section: Methodsmentioning

confidence: 99%

Nonrelapse Mortality and Mycophenolic Acid Exposure in Nonmyeloablative Hematopoietic Cell Transplantation

McDermott

Sandmaier

Storer

et al. 2013

Biology of Blood and Marrow Transplantation

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We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplant. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (N=132) or unrelated (N=176) donors, and received post-grafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in nine patients, eight of whom had a total MPA Css less than 3 μg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades 3–4 acute graft versus host disease (aGVHD) and increased non-relapse mortality, but not with day 28 T-cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 μg/mL could lower grades 3–4 aGVHD and non-relapse mortality in patients receiving an unrelated donor graft.

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Section: Methodsmentioning

confidence: 99%

Nonrelapse Mortality and Mycophenolic Acid Exposure in Nonmyeloablative Hematopoietic Cell Transplantation

McDermott

Sandmaier

Storer

et al. 2013

Biology of Blood and Marrow Transplantation

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“…MPA and MPAG concentrations in the patient plasma samples were measured by HPLC UV assay as previously described with modifications. 20 , 21 HPLC separations of MPA and MPAG were performed independently. Briefly, the separation was achieved using an ERC ODS-1161 column (6 × 100 mm; Yokohamarika Co., Yokohama Japan).…”

Section: Methodsmentioning

confidence: 99%

Development of a Formula to Correct Particle-Enhanced Turbidimetric Inhibition Immunoassay Values so That it More Precisely Reflects High-Performance Liquid Chromatography Values for Mycophenolic Acid

Nakano

Iwami

Yamada

et al. 2018

Transplantation Direct

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BackgroundMycophenolic acid (MPA) concentration measured by homogeneous particle-enhanced turbidimetric inhibition immunoassay (PETINA) may be overestimated due to its cross-reactivity with pharmacologically inactive MPA glucuronide (MPAG), as well as other minor metabolites, accumulated with renal function impairment or co-administered cyclosporine A. In contrast, high-performance liquid chromatography (HPLC) is precise because it can exclude the cross-reactivity. In this study, we assumed HPLC values for MPA (HPLC-MPA) as a reference and aimed to develop a formula correcting PETINA values for MPA (PETINA-MPA) to more precisely reflect HPLC-MPA.MethodsMPA trough concentrations were measured both by HPLC-UV and PETINA in 39 samples issued from 39 solid-organ transplant recipients. MPAG concentrations were also measured using HPLC UV assay. We determined the impacts of renal function and coadministered calcineurin inhibitor on concentrations of MPA and MPAG measured by HPLC. Then, we evaluated the difference between PETINA-MPA and HPLC-MPA. Finally, we develop a formula to reflect HPLC-MPA by using multilinear regression analysis.ResultsMPAG concentration was negatively correlated with estimated glomerular filtration rate (eGFR) (R2 = 0.376, P < 0.001), although MPA was not correlated with eGFR. There were no significant differences in MPA or MPAG concentrations per dose between the patients who were co-administered tacrolimus versus cyclosporine A. Finally, we developed the formulas to reflect HPLC-MPA:Formula 1: Estimated MPA concentration = 0.048 + 0.798 × PETINA‐MPAFormula 2: Estimated MPA concentration = − 0.059 + 0.800 × PETINA‐MPA + 0.002 × eGFRHowever, there was no significant improvement in the coefficient of determination with addition of eGFR in the formula, suggesting that HPLC-MPA can be well predicted by only 1 variable, PETINA-MPA.ConclusionsThis study developed a formula so that PETINA-MPA can be corrected to more precisely reflect HPLC-MPA.

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“…Subsequently, assays employing high-pressure liquid chromatography (HPLC) and more recently tandem mass spectrometry (MS/MS) have become standard for the assessment of the levels of MPA and its metabolites including MPAG. These assays measure total MPA levels including both free and bound fractions [11,12].…”

Section: Measuring Levels Of Mycophenolic Acid and Its Metabolitesmentioning

confidence: 99%

The use of mycophenolate mofetil area under the curve

Chakrabarti

Frame

Abbas

et al. 2021

Current Opinion in Rheumatology

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Purpose of reviewAlthough mycophenolate mofetil (MMF) has been used successfully to treat a myriad of autoimmune diseases, its complex pharmacokinetics make it difficult to determine the true drug exposure for an individual patient. This review summarizes the body of literature focused on the gold standard measurement of the area under the curve (AUC) of mycophenolic acid (MPA), the active metabolite of MMF. Recent findingsFixed dosing of MMF leads to highly variable drug exposure. Retrospective series have reported improved clinical outcomes when a minimum AUC value from 0 to 12 h (AUC 0-12h ) !30 mg h/l is achieved. MPA levels are affected by various drug interactions, hypoalbuminemia, and renal insufficiency and the measurement of free rather than total MPA levels is prudent in some situations. A limited number of studies employing prospective dose adjustment of MMF based on AUC 0-12h measurements have yielded mixed results. SummaryGiven the wide range of MPA AUC encountered in autoimmune diseases, dose adjustments of MMF based on AUC rather than fixed dosing of MMF should be considered in both clinical practice and clinical trials. Limited sampling strategies have been proposed to improve clinical feasibility of measurements, but a standard is yet to be defined.

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Manual and automated (robotic) high-performance liquid chromatography methods for the determination of mycophenolic acid and its glucuronide conjugate in human plasma

Cited by 110 publications

References 5 publications

Nonrelapse Mortality and Mycophenolic Acid Exposure in Nonmyeloablative Hematopoietic Cell Transplantation

Nonrelapse Mortality and Mycophenolic Acid Exposure in Nonmyeloablative Hematopoietic Cell Transplantation

Development of a Formula to Correct Particle-Enhanced Turbidimetric Inhibition Immunoassay Values so That it More Precisely Reflects High-Performance Liquid Chromatography Values for Mycophenolic Acid

The use of mycophenolate mofetil area under the curve

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