Self-Classified Topic Area(s): Small Molecules / Tox / TDM
Development and Evaluation of a LC-MS/MS Method for the Quantitation of Isavuconazole in Human Serum Samples
Andreas Meinitzer, Sieglinde Zelzer, Robert Krause, Markus Herrmann, Dietmar Enko Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
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Andreas Meinitzer (Presenter) Medical University Graz
Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
Background: Therapeutic drug monitoring of isavuconazole, which is a novel broad spectrum antimycoticum against invasive fungal infections, ensures an effective exposure of the drug and minimizes the risk of toxicity (1). The aim of the present study was to evaluate a widely applicable LCMS method eligible for the clinical routine use for the quantification of isavuconaole.
Methods: The method was performed on a Voyager TSQ Quantum triple quadrupole instrument equipped with an Ultimate 3000 chromatography system (Thermo Instruments, San Jose, California, USA). Isavuconazole and the deuterated internal standard d4-isavuconazole were kindly provided by Basilea (Basel, Switzerland). A calibration curve was prepared using plasma samples spiked with six different isavuconazole concentrations ranging from 0.2–12.8 mg/L. The intra-day and the inter-day precision were assessed by replicate analysis (n=5) of three isavuconazol concentrations on the same day and on five consecutive days. Additionally, we investigated lower limit of detection (LOD), the lower limit of quantification (LLOQ), the recovery and preanalytical requirements.
Results: Calibration curves were linear throughout the selected ranges. The correlation coefficient (r²) always exceeded 0.99. The lower limit of quantification (LLOQ) was 0.05 mg/L. Within- and between assay CVs were between 1.4 – 2.9% and 1.5 -3.0%, respectively. The recovery ranged between 94 to 103 %. At room temperature serum samples were stable for five days.
Conclusion: The evaluated method is a precise and well suited diagnostic tool for the therapeutic drug monitoring of isavuconazole in clinical routine.
(1) Jenks JD, Mehta SR, Hoenigl M. Broad spectrum triazoles for invasive mould infections in adults: Which drug and when?. Med Mycol. 2019: 57; S168-S178.
= Discovery stage.
= Translation stage.
= Clinically available.
