TY - JOUR
T1 - Simultaneous analysis of drugs administered to lung-transplanted patients using liquid chromatography–tandem mass spectrometry for therapeutic drug monitoring
AU - Takasaki, Shinya
AU - Hirasawa, Tensei
AU - Sato, Yu
AU - Maekawa, Masamitsu
AU - Tsukamoto, Taku
AU - Kikuchi, Masafumi
AU - Ogura, Jiro
AU - Hayakawa, Yoshihiro
AU - Matsuda, Yasushi
AU - Oishi, Hisashi
AU - Sado, Tetsu
AU - Noda, Masafumi
AU - Okada, Yoshinori
AU - Yamaguchi, Hiroaki
AU - Mano, Nariyasu
N1 - Publisher Copyright:
© 2021 John Wiley & Sons, Ltd.
PY - 2021/6
Y1 - 2021/6
N2 - Several drugs are administered to lung-transplanted patients, which are monitored using therapeutic drug monitoring (TDM). Therefore, we developed and validated a liquid chromatography–tandem mass spectrometry method to simultaneously analyze immunosuppressive drugs such as mycophenolic acid, antifungal drugs such as voriconazole and itraconazole, and its metabolite hydroxyitraconazole. Chromatographic separation was achieved using a C18 column and gradient flow of mobile phase comprising 20 mM aqueous ammonium formate and 20 mM ammonium formate-methanol solution. A simple protein precipitation treatment was performed using acetonitrile/methanol and mycophenolic acid-2H3, voriconazole-2H3, itraconazole-2H4, and hydroxyitraconazole-2H4 as internal standards. The linearity ranges of mycophenolic acid, voriconazole, itraconazole, and hydroxyitraconazole were 100–20,000, 50–10,000, 5–1000, and 5–1000 ng/mL, respectively. The retention time of each target was less than 2 min. The relative errors in intra- and inter-day were within ±7.6%, the coefficient of variation was 8.9% or less for quality control low, medium, and high, and it was 15.8% or less for lower limit of quantitation. Moreover, the patient samples were successfully quantified, and they were within the linear range of measurements. Therefore, our new method may be useful for TDM in lung-transplanted patients.
AB - Several drugs are administered to lung-transplanted patients, which are monitored using therapeutic drug monitoring (TDM). Therefore, we developed and validated a liquid chromatography–tandem mass spectrometry method to simultaneously analyze immunosuppressive drugs such as mycophenolic acid, antifungal drugs such as voriconazole and itraconazole, and its metabolite hydroxyitraconazole. Chromatographic separation was achieved using a C18 column and gradient flow of mobile phase comprising 20 mM aqueous ammonium formate and 20 mM ammonium formate-methanol solution. A simple protein precipitation treatment was performed using acetonitrile/methanol and mycophenolic acid-2H3, voriconazole-2H3, itraconazole-2H4, and hydroxyitraconazole-2H4 as internal standards. The linearity ranges of mycophenolic acid, voriconazole, itraconazole, and hydroxyitraconazole were 100–20,000, 50–10,000, 5–1000, and 5–1000 ng/mL, respectively. The retention time of each target was less than 2 min. The relative errors in intra- and inter-day were within ±7.6%, the coefficient of variation was 8.9% or less for quality control low, medium, and high, and it was 15.8% or less for lower limit of quantitation. Moreover, the patient samples were successfully quantified, and they were within the linear range of measurements. Therefore, our new method may be useful for TDM in lung-transplanted patients.
KW - LC–MS/MS
KW - human plasma
KW - lung transplantation
KW - therapeutic drug monitoring
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U2 - 10.1002/bmc.5067
DO - 10.1002/bmc.5067
M3 - Article
C2 - 33450064
AN - SCOPUS:85099750258
SN - 0269-3879
VL - 35
JO - Biomedical Chromatography
JF - Biomedical Chromatography
IS - 6
M1 - e5067
ER -