Arzneimittelforschung 2008; 58(7): 348-352
DOI: 10.1055/s-0031-1296518
Immunomodulators · Immunostimulants · Immunosuppressants
Editio Cantor Verlag Aulendorf (Germany)

High-performance Liquid Chromatography Method for the Determination of Mycophenolic Acid in Human Plasma and Application to a Pharmacokinetic Study of Mycophenolic Acid Dispersible Tablet

Wei Zhang
1   Center for Instrumental Analysis, China Pharmaceutical University (Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education), Nanjing, People’s Republic China
Bing-ren Xiang
1   Center for Instrumental Analysis, China Pharmaceutical University (Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education), Nanjing, People’s Republic China
Jing Zhang
2   Jiangsu Provincial People’s Hospital, Nanjing, People’s Republic China
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15. Dezember 2011 (online)


A sensitive and selective high-performance liquid chromatographic-ultraviolet (HPLC-UV) method for the determination of mycophenolic acid (MPA, CAS 24280-93-1) in human plasma has been developed. Sample treatment was based on protein precipitation with a trichloroacetic acid-water (10:90, w/v) solution. The analytical determination was carried out by HPLC with ultraviolet detection at 254 nm. Chromatographic separation was achieved on a C18 column by isocratic elution with acetonitrile-water (pH 4.4) (50:50, v/v) at a flow rate of 1.0 mL/min. The method was linear in the concentration range of 0.2–50.0 μg/mL. The lower limit of quantification (LLOQ) was 0.2 μg/mL. The intra-day and inter-day relative standard deviations across three validation runs over the entire concentration range were less than 7.05%. The accuracy determined at three concentrations (0.4, 5.0 and 20.0 μg/mL for MPA) was within ± 10.0%. The method was successfully applied to the evaluation of the pharmacokinetic profile of MPA dispersible tablet in 20 healthy volunteers. The results showed that AUC, Cmax and T1/2 for the test and reference formulations were not significantly different (P > 0.05). The relative bioavailability was 96.42 ± 15.5%.

  • References

  • 1 Sollinger HW. Mycophenolates in transplantation. Clin Transplant. 2004; 18: 485-492
  • 2 Pisupati J, Jain A, Burckart G, Hamad I, Zuckerman S, Fung J et al. Intraindividual and Interindividual Variations in the Pharmacokinetics of Mycophenolic Acid in Liver Transplant Patients. J Clin Pharmacol. 2005; 45: 34-41
  • 3 Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000; 47: 85-118
  • 4 Morris RE. Mechanisms of action of new immunosuppressive drugs. Kidney Int Suppl. 1996; 53: 26-38
  • 5 Bullingham R, Monroe S, Nicholls A, Hale M. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration. J Clin Pharmacol. 1996; 36: 315-324
  • 6 Jacobson P, Rogosheske J, Barker JN, Green K, Ng J, Weis-dorf D et al. Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation. Clin Pharmacol Ther. 2005; 78: 486-500
  • 7 Borrows R, Chusney G, Loucaidou M, James A, Lee J, Tromp JV et al. Mycophenolic Acid 12-h Trough Level Monitoring in Renal Transplantation: Association with Acute Rejection and Toxicity. Am J Transplant. 2006; 6: 121-128
  • 8 Patel CG, Akhlaghi F. High-performance liquid chromatography method for the determination of mycophenolic acid and its acyl and phenol glucuronide metabolites in human plasma. Ther Drug Monit. 2006; 28: 116-122
  • 9 Benoit-Biancamano MO, Caron P, Lévesque E, Delage R, Couture F, Guillemette C. Sensitive high-performance liquid chromatography - tandem mass spectrometry method for quantitative analysis of mycophenolic acid and its glucuronide metabolites in human plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 24: 159-167
  • 10 Kleinbaum DG, Kupper LL, Nizam A. Applied regression analysis and other multivariable methods. 3rd ed Pacific Grove: Duxbury Press; 1998