Premium
Simultaneous analysis of drugs administered to lung‐transplanted patients using liquid chromatography–tandem mass spectrometry for therapeutic drug monitoring
Author(s) -
Takasaki Shinya,
Hirasawa Tensei,
Sato Yu,
Maekawa Masamitsu,
Tsukamoto Taku,
Kikuchi Masafumi,
Ogura Jiro,
Hayakawa Yoshihiro,
Matsuda Yasushi,
Oishi Hisashi,
Sado Tetsu,
Noda Masafumi,
Okada Yoshinori,
Yamaguchi Hiroaki,
Mano Nariyasu
Publication year - 2021
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.5067
Subject(s) - chemistry , chromatography , ammonium formate , therapeutic drug monitoring , protein precipitation , itraconazole , voriconazole , mass spectrometry , liquid chromatography–mass spectrometry , coefficient of variation , pharmacology , drug , antifungal , medicine , dermatology
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‐ 2 H 3 , voriconazole‐ 2 H 3 , itraconazole‐ 2 H 4 , and hydroxyitraconazole‐ 2 H 4 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.