Inclusion of MPA and in a rapid multi-drug LC–tandem mass spectrometric method for simultaneous determination of immunosuppressants

Ceglarek, Uta; Casetta, Bruno; Lembcke, Jan; Baumann, Sven; Fiedler, Georg Martin; Thiery, Joachim

doi:10.1016/j.cca.2006.05.019

Cited by 44 publications

(27 citation statements)

References 14 publications

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“…The LOQ corresponded to a concentration of 0.72 mg/mL, as previously defined. If we consider a typical range of the 0-12 h AUC curve (7.3-102.3 mg/h/mL) [31], the obtained RSD value was below 15%, comparable to those reported by other authors for HPLC methods [34]. …”

Section: Assessment Of Performance Characteristicssupporting

confidence: 79%

Development of a CE method for the determination of mycophenolic acid in human plasma: A comparison with HPLC

et al. 2007

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Mycophenolate mofetil (MMF) is a widely used drug for the maintenance of immunosuppressive therapy in renal-transplant recipients. MMF is rapidly metabolized in vivo to mycophenolic acid (MPA), a reversible, noncompetitive inhibitor of inosine monophosphate dehydrogenase, which represents a limiting enzyme in lymphocyte proliferation. MPA shows large interindividual pharmacokinetic variability: its monitoring is therefore of primary importance to achieve adequate immunosuppression with minimized risk of graft rejection or toxicity. We developed a CE method for the determination of total MPA (tMPA) in plasma, based on easy sample preparation; CE evaluation of tMPA was performed in 30 mmol/L sodium-borate with 10 mmol/L SDS (pH 10.00) at 25 degrees C using a 60 cm (54.5 to window) uncoated capillary with UV detection at 254 nm wavelength. MPA was readily detectable in plasma; the CE method was linear in the range of 0.7-120 microg/mL (r >0.992). Intra- and interassay imprecision was <7% except for the lowest spiked MPA concentration, which had an intra-assay RSD% of 14.7 compared to 18.3 interassay. Data by CE were compared with results obtained by a validated HPLC method. CE assay of tMPA exhibited a very good correlation (r(2) >0.988) with respect to HPLC; Bland-Altman difference versus average showed a mean of -0.18 microg/mL +/- 1.14 SD. CE determination of tMPA is a robust, sensitive and reproducible method with the advantage over HPLC of being fast, simple and unexpensive, also enabling quick assessment of MPA for pharmacokinetic studies.

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Section: Assessment Of Performance Characteristicssupporting

confidence: 79%

Development of a CE method for the determination of mycophenolic acid in human plasma: A comparison with HPLC

et al. 2007

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“…Some salient features of the method included: (a) adequate chromatographic separation between MPAG and MPA to avoid in-source cross-talk owing to fragmentation of MPAG to MPA by the use of a POROS pre-column, which also helped in matrix cleanup; (b) the use of cyclosporine D as IS for both MPA and MPAG; (c) efficient optimization of the ionization interfering effects owing to MPAG as a result of solvent change in the column switching program; and (d) adoptability of the method for quantitation of MPA and other immunosuppressant drugs in a single run after column switching to exclude MPAG (Ceglarek et al, 2006). Difrancesco et al (2007 have developed a LC-MS/MS assay for measuring MPA and MPAG along with cortisol, dexamethasone, methylprednisolone, prednisone and prednisolone, which are also part of immunosuppressive therapy in transplantation patients.…”

Section: Measurement Of Mpa In Vitreous Humormentioning

confidence: 99%

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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“…This allows a flow of up to 5 mL/min during extraction at a back pressure <100 bar. As a result on-line sample preparation can be adapted to high throughput conditions [32][33][34]. Advantages of this approach are the possibilities for identification and quantification, high analytical detection power, as well as high accuracy and reproducibility.…”

Section: Spementioning

confidence: 99%

Applications of LC‐MS/MS in Clinical Laboratory Diagnostics

Ceglarek

Fiedler

Thiery

2012

Analytical Techniques for Clinical Chemistry

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Inclusion of MPA and in a rapid multi-drug LC–tandem mass spectrometric method for simultaneous determination of immunosuppressants

Cited by 44 publications

References 14 publications

Development of a CE method for the determination of mycophenolic acid in human plasma: A comparison with HPLC

Development of a CE method for the determination of mycophenolic acid in human plasma: A comparison with HPLC

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

Applications of LC‐MS/MS in Clinical Laboratory Diagnostics

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