Pharmacokinetic study of isavuconazonium in human plasma measured by HPLC-MS/MS and its use in healthy Chinese subjects

• Published in: Bioanalysis p. 1
• Main Authors: Qiu, Linlin, Lin, Jie, Su, Yuchen, Kong, Yifu, Zhou, Yanli, Chen, Yifang, Yu, Yonghua
• Format: Journal Article
• Language: English
• Published: England 19.08.2025
• Subjects: method validation; Isavuconazonium sulfate; HPLC-MS/MS; pharmacokinetic; human plasma
• ISSN: 1757-6199
• DOI: 10.1080/17576180.2025.2548195

To establish a rapid, sensitive HPLC-MS/MS method for quantifying isavuconazonium in human plasma and characterize its pharmacokinetics in healthy Chinese subjects under fasting and postprandial conditions. Plasma samples were processed via acetonitrile protein precipitation. Separation was performed on an LC-20ADXR Plus C18 column with gradient elution (0.01% formic acid/acetonitrile). Detection used a Triple Quad 4500 mass spectrometer with MRM; isavuconazole-d4 was the internal standard. The method was validated, then applied to a crossover study in 32 healthy subjects (fasting vs. postprandial). The method showed good linearity (4-4000 ng/mL, R ≥0.9801) with LLOQ 4 ng/mL. Stability was confirmed under various conditions (e.g. 53 days at -20°C, 66 days at -80°C). Pharmacokinetic results revealed food delayed Tmax (2.5 vs. 5.0 h) and reduced Cmax (1929.68 vs. 1300.17 ng/mL) but did not affect AUC . The validated HPLC-MS/MS method is rapid and reliable for therapeutic drug monitoring. Food affects absorption but not total exposure, guiding clinical dosing in Chinese populations.