Key Takeaways & Executive Findings
- •• Developed a rapid and sensitive LC-MS/MS method for isavuconazole quantification in human plasma with a lower limit of quantification of 5 ng/mL. • Validated the method according to FDA guidelines, achieving high precision (RSD < 9.2%) and accuracy (RE within ±4.5%). • Successfully applied the method to a pharmacokinetic study in healthy Chinese volunteers, providing key PK parameters. • The method is suitable for therapeutic drug monitoring and clinical pharmacokinetic studies of isavuconazole.
Abstract
A rapid, sensitive, and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of isavuconazole in human plasma. Sample preparation involved a simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a C18 column using a gradient elution with a mobile phase consisting of 0.1% formic acid in water and acetonitrile. The method was validated over a linear range of 5.00-5000 ng/mL with a lower limit of quantification of 5.00 ng/mL. The intra- and inter-run precision (relative standard deviation, RSD) were less than 8.5% and 9.2%, respectively, and accuracy (relative error, RE) ranged from -3.2% to 4.5%. The method was successfully applied to a pharmacokinetic study in healthy Chinese volunteers after oral administration of isavuconazole. The key pharmacokinetic parameters, including maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC), were determined. The results demonstrated that the method is suitable for therapeutic drug monitoring and pharmacokinetic studies of isavuconazole.
1. Introduction
Isavuconazole is a novel triazole antifungal agent with broad-spectrum activity against Aspergillus, Candida, and Mucorales species. It is approved for the treatment of invasive aspergillosis and mucormycosis. Therapeutic drug monitoring (TDM) of isavuconazole is recommended due to its variable pharmacokinetics and exposure-response relationships. Therefore, a reliable and sensitive analytical method is essential for quantifying isavuconazole in biological matrices.
Several methods have been reported for the quantification of isavuconazole in human plasma, including high-performance liquid chromatography with ultraviolet detection (HPLC-UV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, some of these methods suffer from long run times, complex sample preparation, or lack of sensitivity. In this study, we developed and validated a simple, rapid, and sensitive LC-MS/MS method for the quantification of isavuconazole in human plasma using a protein precipitation extraction procedure. The method was fully validated according to the FDA guidelines and successfully applied to a pharmacokinetic study in healthy Chinese volunteers.
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ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang (2025). Development and Validation of a Novel Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Isavuconazole in Human Plasma and Its Application to a Pharmacokinetic Study. Chinese Journal of New Drugs. https://doi.org/cast_zgxyzz_1236731781714596256
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Frequently Asked Questions
What is the purpose of this study?
The purpose of this study was to develop and validate a rapid and sensitive LC-MS/MS method for the quantification of isavuconazole in human plasma and to apply it to a pharmacokinetic study in healthy Chinese volunteers.
What is the lower limit of quantification (LLOQ) of the developed method?
The lower limit of quantification (LLOQ) of the developed method is 5.00 ng/mL.
What sample preparation technique was used?
A simple protein precipitation with acetonitrile was used for sample preparation.
What were the key pharmacokinetic parameters determined in the study?
The key pharmacokinetic parameters determined included maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC).
Is the method suitable for therapeutic drug monitoring?
Yes, the method is suitable for therapeutic drug monitoring and pharmacokinetic studies of isavuconazole due to its sensitivity, accuracy, and precision.
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