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

Abstract

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.

Enhanced detection in capillary electrophoresis: Example determination of serum mycophenolic acid

“…2). The analytical aspects of both methods are comparable with those of sample handling and analysis time in this study and in a previous one [20]. Figure 3 illustrates the analysis of a standard and the same patient by both CE and HPLC.…”

“…Ünsalan et al [19] have used CZE after sample evaporation to improve the sensitivity, while Carlucci et al [20] have used MEKC for MPA determination after protein removal with acetonitrile or acids. To improve the detection level of this drug in serum, stacking on the capillary is desirable as a simple method.…”

Determination of mycophenolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry

“…Several methods have been reported for the analysis of MPA and its metabolites in different biological fluids by electrophoresis [11] , [12] , [13] , [14] , immunoassay technique [15] , [16] , [17] , high performance liquid chromatography using diode array [18] , fluorescence [19] , [20] , [21] , UV [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , and mass spectrometry detection [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] . Relatively few UPLC–MS/MS based methods are available in literature for rapid analysis of MPA in biological samples [42] , [43] .…”

Development of HPLC‐UV method for rapid and sensitive analysis of topically applied tetracaine: its comparison with a CZE method

“…Although the imprecision was higher, the lower operation costs and volume of electrolyte used, and the faster running time, made CE preferable to HPLC for this kind of study. This observation is in agreement with those of other authors in comparisons of the two methods (Clohs and McErlane, ; Aurora Prado et al ., ; Muscarella et al ., ; Carlucci et al ., ; Kowalski and Plenis, ; Kocevar et al ., ). Sometimes HPLC was not useful (Hilz et al ., ), owing to the physicochemical properties of the analyte resulting in poor resolution and reproducibility (Bexheti et al ., ).…”