TY - JOUR
T1 - Development of a precise quantitative method for monitoring sirolimus in whole blood using LC/ESI–MS/MS
AU - Shigeta, Kensuke
AU - Kikuchi, Masafumi
AU - Tanaka, Masaki
AU - Takasaki, Shinya
AU - Oishi, Hisashi
AU - Sado, Tetsu
AU - Matsuda, Yasushi
AU - Noda, Masafumi
AU - Okada, Yoshinori
AU - Mano, Nariyasu
AU - Yamaguchi, Hiroaki
N1 - Publisher Copyright:
© 2020 John Wiley & Sons, Ltd.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
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U2 - 10.1002/bmc.4853
DO - 10.1002/bmc.4853
M3 - Article
C2 - 32302012
AN - SCOPUS:85085035624
SN - 0269-3879
VL - 34
JO - Biomedical Chromatography
JF - Biomedical Chromatography
IS - 8
M1 - e4853
ER -