Development and Validation of A Liquid Chromatography-Tandem Mass Spectrometry Method to Simultaneously Measure Tacrolimus and Everolimus Concentrations in Kidney Allograft Biopsies after Kidney Transplantation

Mengyu Zhang, Soichiro Tajima, Tomohiro Shigematsu, Hiroshi Noguchi, Keizo Kaku, akihiro tsuchimoto, Yasuhiro Okabe, Nobuaki Egashira, Ichiro Ieiri

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background:Therapeutic drug monitoring is necessary for immunosuppressive therapy with tacrolimus and everolimus after kidney transplantation. Several studies have suggested that the concentrations of immunosuppressive agents in allografts may better reflect clinical outcomes than whole blood concentrations. This study aimed to develop a method for the simultaneous quantification of tacrolimus and everolimus concentrations in clinical biopsy samples and investigate their correlation with histopathological findings in kidney transplant recipients.Methods:Fourteen biopsy samples were obtained from kidney transplant recipients at 3 months after transplantation. Kidney allograft concentrations (Ctissue) of tacrolimus and everolimus were measured by liquid chromatography-tandem mass spectrometry, and the corresponding whole blood trough concentrations (C0) were obtained from clinical records.Results:The developed method was validated over a concentration range of 0.02-2.0 ng/mL for tacrolimus and 0.04-4.0 ng/mL for everolimus in kidney tissue homogenate. The Ctissueof tacrolimus and everolimus in kidney biopsies ranged from 21.0 to 86.7 pg/mg tissue and 33.5-105.0 pg/mg tissue, respectively. Dose-adjusted Ctissueof tacrolimus and everolimus was significantly correlated with the dose-adjusted C0(P < 0.0001 and P = 0.0479, respectively). No significant association was observed between the Ctissueof tacrolimus and everolimus and the histopathologic outcomes at 3 months after transplantation.Conclusions:This method could support further investigation of the clinical relevance of tacrolimus and everolimus allograft concentrations after kidney transplantation.

Original languageEnglish
Pages (from-to)275-281
Number of pages7
JournalTherapeutic drug monitoring
Volume44
Issue number2
DOIs
Publication statusPublished - Apr 1 2022

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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