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

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2025-08-01 Epub Date: 2025-08-19 DOI:10.1080/17576180.2025.2548195

Linlin Qiu, Jie Lin, Yuchen Su, Yifu Kong, Yanli Zhou, Yifang Chen, Yonghua Yu

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引用次数: 0

Abstract

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, R² ≥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_0-t.

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.

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HPLC-MS/MS法测定异唑康唑在人血浆中的药动学研究及其在中国健康人群中的应用。

目的：建立一种快速、灵敏的HPLC-MS/MS定量人血浆中异唑康唑的方法，并表征其在空腹和餐后条件下的药代动力学。材料与方法：血浆样品经乙腈蛋白沉淀法处理。色谱柱为LC-20ADXR Plus C18，梯度洗脱（0.01%甲酸/乙腈）。检测采用带MRM的Triple Quad 4500质谱仪；内标为依沙乌康唑-d4。该方法经过验证，然后应用于32名健康受试者（空腹与餐后对照）的交叉研究。结果：该方法线性良好（4 ~ 4000 ng/mL, R2≥0.9801），定量限为4 ng/mL。在各种条件下（例如，在-20°C下53天，在-80°C下66天）证实了稳定性。药代动力学结果显示，食物延迟Tmax （2.5 vs. 5.0 h）和降低Cmax (1929.68 vs. 1300.17 ng/mL)，但不影响AUC0-t。结论：经验证的HPLC-MS/MS方法用于治疗药物监测快速、可靠。食物影响吸收，但不影响总暴露量，指导中国人群的临床剂量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.