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Development of a precise quantitative method for monitoring sirolimus in whole blood using LC/ESI–MS/MS
Author(s) -
Shigeta Kensuke,
Kikuchi Masafumi,
Tanaka Masaki,
Takasaki Shinya,
Oishi Hisashi,
Sado Tetsu,
Matsuda Yasushi,
Noda Masafumi,
Okada Yoshinori,
Mano Nariyasu,
Yamaguchi Hiroaki
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4853
Subject(s) - sirolimus , chromatography , chemistry , therapeutic drug monitoring , electrospray ionization , whole blood , ion suppression in liquid chromatography–mass spectrometry , liquid chromatography–mass spectrometry , tandem mass spectrometry , quantitative analysis (chemistry) , mass spectrometry , pharmacokinetics , pharmacology , surgery , medicine , biochemistry
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.