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

Aims: 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.

Materials & Methods: 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).

Results: 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.

Conclusions: 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.