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Comparison of plasma and oral fluid concentrations of mycophenolic acid and its glucuronide metabolite by LC-MS in kidney transplant patients

  • Pâmela C. Lukasewicz FerreiraEmail author
  • Flavia Valladao Thiesen
  • Thaina Tavares de Araujo
  • Domingos Otávio D’Ávila
  • Giovani Gadonski
  • Carmem Silvana A. de Oliveira
  • Aline Rigon Zimmer
  • Pedro Eduardo Fröehlich
Pharmacokinetics and Disposition

Abstract

Purpose

Mycophenolic acid is one of the most used immunosuppressive drugs in solid organ transplant treatments in the world. Developing a highly sensitive analytical method to analyse the drug and its metabolites in oral fluid and plasma is important to evaluate the possibility of using oral fluid as a biological matrix in therapeutic drug monitoring, instead of plasma.

Method

The liquid chromatography coupled to mass spectrometry (LC-MS) method was developed and validated for determining mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) in oral fluid and plasma, with both matrices presenting a detection limit of 1 ng/mL for MPA and 5 ng/mL for MPAG. Both analytes were analysed after a simple protein precipitation procedure. Transplanted-kidney samples of oral fluid and blood were collected from 13 patients that were hospitalised and kept at − 80 °C until analyses.

Results

The proposed method was linear in the concentration range of 5–500 ng/mL for MPA and 10–500 ng/mL for MPAG, with correlation coefficients (r) between 0.9925 and 0.9973. It was then applied to samples collected from kidney-transplanted patients and used for calculation of pharmacokinetics parameters.

Conclusion

After comparing plasma and oral fluid concentrations as well as performing a non-compartmental pharmacokinetic analysis of the average curves, it is possible to suggest that oral fluid concentration may be used as an alternative for MPA and MPAG monitoring in kidney transplant patients.

Keywords

LC-MS Oral fluid Plasma Mycophenolic acid Mycophenolic acid glucuronide Pharmacokinetic 

Notes

Acknowledgments

The authors wish to thank CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and PPGCF-UFRGS (the Postgraduate Program in Pharmaceutical Sciences - Federal University of Rio Grande do Sul) for the financial support, and the team on the 7th floor, especially the nurses, of Hospital São Lucas da PUC for their support and availability to perform the sample collections.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2018_2614_MOESM1_ESM.docx (23 kb)
ESM 1 (DOCX 23 kb)
228_2018_2614_MOESM2_ESM.pptx (80 kb)
ESM 2 (PPTX 80 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Pâmela C. Lukasewicz Ferreira
    • 1
  • Flavia Valladao Thiesen
    • 2
  • Thaina Tavares de Araujo
    • 2
  • Domingos Otávio D’Ávila
    • 3
  • Giovani Gadonski
    • 4
  • Carmem Silvana A. de Oliveira
    • 3
  • Aline Rigon Zimmer
    • 1
  • Pedro Eduardo Fröehlich
    • 1
  1. 1.Programa de Pós Graduação em Ciências FarmacêuticasUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Pontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  3. 3.Centro de Pesquisa ClínicaHospital São Lucas da PUCPorto AlegreBrazil
  4. 4.Clínica MedicaHospital São Lucas da PUCPorto AlegreBrazil

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