Development of a precise quantitative method for monitoring sirolimus in whole blood using LC/ESI–MS/MS

Kensuke Shigeta, Masafumi Kikuchi, Masaki Tanaka, Shinya Takasaki, Hisashi Oishi, Tetsu Sado, Yasushi Matsuda, Masafumi Noda, Yoshinori Okada, Nariyasu Mano, Hiroaki Yamaguchi

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1 Citation (Scopus)

Abstract

Sirolimus is used on patients after solid organ transplantation and on lymphangioleiomyomatosis (LAM) patients, and therapeutic drug monitoring is required in clinical practice. We have previously reported an accurate method for quantitative determination of sirolimus, but its sample preparation step was complicated. In this study, we developed a modified liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI–MS/MS) method for sirolimus quantification. A supported liquid extraction cartridge was used to purify sirolimus from whole blood and ion suppression was mostly prevented. The validation results met the acceptance criteria. This method was compared with the antigen conjugated magnetic immunoassay (ACMIA) and our previously reported method, using whole blood samples from LAM patients. Comparison of the Bland–Altman plots of the currently developed method and the previous method revealed no significant difference between the two methods (mean bias, −2.02%; 95% CI, −7.81–3.78). The values obtained using ACMIA were significantly higher than those obtained using the current method by 13.87% (95% CI, 6.49–21.25) owing to cross-reactivity. The degrees of cross reactivities in LAM patients and in organ transplant patients were similar, and our LC/ESI–MS/MS method precisely measured the blood concentrations of sirolimus.

Original languageEnglish
Article numbere4853
JournalBiomedical Chromatography
Volume34
Issue number8
DOIs
Publication statusPublished - 01-08-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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