High-performance liquid chromatographic method for mycophenolic acid and its glucuronide in serum and urine

Teshima, Daisuke; Otsubo, Kenji; Kitagawa, Naoki; Yoshimura, Saburo; Itoh, Yoshinori; Oishi, Ryozo

doi:10.1046/j.1365-2710.2003.00450.x

Cited by 20 publications

(28 citation statements)

References 15 publications

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“…The assay for total MPA utilized protein precipitation with acetonitrile as sample preparation and this was found to be rapid and reliable. While there have been a few previous reports that have utilized simple protein precipitation with methanol or acetonitrile (Elbarbry and Shoker, 2007;Shen et al, 2005;Srivatsan et al, 2004), other studies have used time consuming sample preparation methods including liquid-liquid extraction (Bahrami and Mohammadi, 2006;Na-Bangchang et al, 2000), solid-phase extraction (Brandhorst et al, 2006;Daurel-Receveur et al, 2006;Patel and Akhlaghi, 2006;Teshima et al, 2003;Yin et al, 2006) and protein precipitation with/without evaporation to dryness (Bolon et al, 2004;Indjova et al, 2005;Shipkova et al, 1998Shipkova et al, , 2001Srivatsan et al, 2004). An additional benefit from using this sample preparation technique is the ability to use lower sample volumes of plasma (100 μL), which is of importance when testing children, from whom it is often possible to collect only limited volumes of blood.…”

Section: Discussionmentioning

confidence: 99%

“…For HPLC quantification, reported methods have used UV detection (Bahrami and Mohammadi, 2006;Bolon et al, 2004;Daurel-Receveur et al, 2006;Elbarbry and Shoker, 2007;Indjova et al, 2005;Mandla et al, 2003;Na-Bangchang et al, 2000;Pastore et al, 2002;Patel and Akhlaghi, 2006;Shipkova et al, 1998Shipkova et al, , 2001Srivatsan et al, 2004;Streit et al, 2004;Teshima et al, 2002Teshima et al, , 2003Westley et al, 2005;Yin et al, 2006;Zambonin et al, 2004), including diode array detection (Bolon et al, 2004;Daurel-Receveur et al, 2006;Shipkova et al, 1998) or fluorescence detection (Hosotsubo et al, 2001;Shen et al, 2005). In previous assays, some assays used large sample volumes (>100 μL; Bahrami and Mohammadi, 2006;Bolon et al, 2004;Elbarbry and Shoker, 2007;Shipkova et al, 1998) or time-consuming sample preparation using liquid-liquid extraction (Bahrami and Mohammadi, 2006;Na-Bangchang et al, 2000) or solid-phase extraction (Brandhorst et al, 2006;Daurel-Receveur et al, 2006;Patel and Akhlaghi, 2006;Teshima et al, 2003;Yin et al, 2006), and some had lengthy run times (Bolon et al, 2004;Srivatsan et al, 2004;…”

Section: Introductionmentioning

confidence: 99%

“…There have been a number of previously published assays for total MPA, including assays using HPLC (Atcheson et al, 2004a;Bahrami and Mohammadi, 2006;Brandhorst et al, 2006;Bolon et al, 2004;Daurel-Receveur et al, 2006;Elbarbry and Shoker, 2007;Hosotsubo et al, 2001;Indjova et al, 2005;Mandla et al, 2003;Na-Bangchang et al, 2000;Pastore et al, 2002;Patel and Akhlaghi, 2006;Shen et al, 2005;Shipkova et al, 1998Shipkova et al, , 2001Srivatsan et al, 2004;Streit et al, 2004;Teshima et al, 2002Teshima et al, , 2003Westley et al, 2005;Willis et al, 2000;Yin et al, 2006;Zambonin et al, 2004) and enzyme multiplied immunoassay technique (EMIT; Beal et al, 1998;Weber et al, 2002b) and the details of Acknowledgements Lihua Zeng is supported by NH and MRC Project grant 396702. Christa E. Nath is supported by the Leukaemia Research Support Fund of The Children's Hospital Westmead, and by NH and MRC Project grant 396702.…”

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confidence: 99%

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HPLC‐UV assay for monitoring total and unbound mycophenolic acid concentrations in children

Zeng

Nath

Shaw

et al. 2008

Biomedical Chromatography

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A simple, accurate and sensitive HPLC method was developed for measuring total and unbound mycophenolic acid (MPA) in human plasma. Total MPA was extracted by protein precipitation and ultrafiltration was used to assess unbound MPA concentrations. The supernatant (20 microL) or ultrafiltrate (100 microL) was injected onto a C(18) HPLC column with a mobile phase of 0.05 m sodium phosphate buffer (pH 2.31)-acetonitrile (55:45, v/v for total MPA; 50:50 for unbound MPA) with UV detection at 254 nm. The extraction recovery was over 93% and reproducible. The assay was linear over the concentration range of 0.07-50 mg/L for total MPA and 4-1500 microg/L for unbound MPA. Intra- and inter-day assay reproducibility was less than 10%. Detection limits were 0.04 mg/L and 2 microg/L for total and unbound MPA, respectively. The assay utility was established in samples collected from five paediatric bone marrow transplant recipients who were receiving intravenous doses of mycophenolate mofetil. In these patients MPA concentrations ranged from 0.07 to 7.83 mg/L and unbound drug concentrations ranged from 2.1 to 107.5 microg/L. This method can be effectively applied to MPA pharmacokinetics in paediatric patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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HPLC‐UV assay for monitoring total and unbound mycophenolic acid concentrations in children

Zeng

Nath

Shaw

et al. 2008

Biomedical Chromatography

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“…MPA plasma concentrations were measured by high-performance liquid chromatography (HPLC) [13]. MPA-AUC 0-12h was calculated by the linear trapezoidal method.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Mycophenolic Acid Exposure Using a Limited Sampling Strategy in Renal Transplant Recipients

Liu²,

Huang³

et al. 2013

Am J Nephrol

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Background/Aims: While there are drug exposure equation models based on limited sampling times for mycophenolate mofetil (MMF), there are few for enteric-coated mycophenolate sodium (EC-MPS), and none that studied Chinese individuals. Our objective is to generate the optimal model equations for estimation of the mycophenolic acid (MPA) area under the plasma concentration-time curve from 0 to 12 h (MPA-AUC_0-12h) with a limited sampling strategy (LSS) for renal transplant recipients receiving EC-MPS. Methods: The pharmacokinetics in 31 Chinese renal allograft recipients treated with EC-MPS in combination with tacrolimus and steroids were determined. The model equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC. Results: A total of 31 patients with an average age and weight of 37.58 ± 10.9 years and 60.9 ± 10.7 kg, respectively, were included. Mean serum creatinine and glomerular filtration rate were 112.2 ± 17.7 μmol/l and 65.6 ± 14.6 ml/min, respectively. The mean values of AUC_0-12h, pre-dose MPA trough concentration (C₀), maximum concentrations (C_max), and time to reach C_max (T_max) were 61.17 ± 26.39 mg·h/l (range 22.9-123.0 mg·h/l), 4.98 ± 4.65 mg/l (range 0.13-20.04 mg/l), 17.54 ± 10.67 mg/l (range 4.08-42.36 mg/l), and 5.0 ± 2.6 h (range 1.0-10.5 h), respectively. The best predictive equation for estimation of MPA-AUC_0-12h was -3.63 + 8.35 × C₄ + 17.04 × C₇ + 13.74 × C₁₂ (r² = 0.7491), prediction bias (PE%) was 20.9 ± 20.37, and prediction precision (APE%) was 3.66 ± 29.20. Conclusions: This model provides an effective approach for estimation of full MPA-AUC_0-12h in Chinese adult renal allograft recipients treated with EC-MPS and tacrolimus.

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“…The mobile phase used in the method was a combination of phosphate buffer and acetonitrile (35:65 v/v) pumped at a flow rate of 0.4 mL min -1 . Few HPLC methods were found on the analysis of mycophenolate acid and mycophenolate acid glucuronide in biosamples [22][23][24][25][26][27][28][29][30][31]. These methods used similar mobile phases as reported above and carried out separations on conventional reversed phase columns coupled with mass spectrophotometer.…”

Section: Lc-ms Compatible Stability Indicating Rp-uplc Methods For Thementioning

confidence: 99%

LC-MS Compatible Stability Indicating RP-UPLC Method for the Estimation of Ester Prodrug of Mycophenolic Acid in Injection Formulation

Rao¹,

Krishna²,

Bellam³

et al. 2018

Asian J. Chem.

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This study explores the ultra performance liquid chromatography for the quantification of mycophenolate mofetil (an immunosuppressant agent) in an injection formulation. Mycophenolate mofetil was separated from its seven specified impurities on HSS (high strength silica) C18 column (100 × 2.1 mm, 1.8 µm). The optimized mobile phase is compatible to mass spectrometry and hence the method can be equally run on LC-MS system for mass determinations. Efficient UV detection at 250 nm enabled determination of mycophenolate mofetil with no interference from placebo solution, diluent and other specified and unspecified impurities. The retention time of mycophenolate mofetil in the method was 1.79 min and all other impurities were eluted within in 8 min. The method optimization studies show that the selectivity of mycophenolate mofetil and its impurities was dependent on the type of organic solvent and its elution strength. The method was validated for specificity, linearity, precision, accuracy and robustness in range of 50 to 150 % of target analyte concentration (i.e. 62.50-195.31 µg mL -1 ). The linearity of peak area responses versus concentrations was demonstrated by linear least square regression analysis. An excellent linear relation exists between the concentration and detector response (R 2 > 0.9999). Precision of the test method was proved with a relative standard deviation less than 1.0 %.

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High-performance liquid chromatographic method for mycophenolic acid and its glucuronide in serum and urine

Abstract: The HPLC method described should be useful for the routine monitoring of serum and urine concentrations of MPA and MPAG during immunosuppressive medication for renal transplantation.

Cited by 20 publications

References 15 publications

HPLC‐UV assay for monitoring total and unbound mycophenolic acid concentrations in children

HPLC‐UV assay for monitoring total and unbound mycophenolic acid concentrations in children

Evaluation of Mycophenolic Acid Exposure Using a Limited Sampling Strategy in Renal Transplant Recipients

LC-MS Compatible Stability Indicating RP-UPLC Method for the Estimation of Ester Prodrug of Mycophenolic Acid in Injection Formulation

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