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| Determination of antifungal drug concentrations of voriconazole, posaconazole, and amphotericin B using liquid chromatography-mass spectrometry |
| CHEN Ming, LIU Zhen, HUANG Xiaowu |
| Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing 100091, China |
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Abstract Objective To establish a high-performance liquid chromatography-tandem mass spectrometry method for antifungal drug concentration determination of voriconazole, posaconazole and amphotericin B so as to meet the needs of routine therapeutic drug monitoring in clinical practice. Methods The chromatography was performed using Agilent Poroshell 120SB C18 chromatography column (4.6 mm×50 mm, 2.7 μm). The mobile phase was methanol/0.2% acetic acid solution, with gradient elution. The mass spectrometry was carried out using an electrospray ion source, multiple reaction monitoring (MRM), and positive ion mode. Acetaminophen was used as the internal standard, voriconazole: m/z 350.1→281.3, posaconazole: m/z 701.2→127.0, amphotericin B: m/z 924.0→743.1, acetaminophen: m/z 152.0→110.0. The sample was first subjected to protein precipitation with methanol before injection analysis, with an injection volume of 5 μl. The analysis time was 9.0 minutes. Results There was no interference to the determination of endogenous substances in the samples, and the three drugs had good linear relationships within their respective linear ranges, with r values greater than 0.997. The precision (RSD) and accuracy (RE) of the high, medium, and low quality control samples of the three drugs were all less than 10%, and the recovery rates were all above 90%. The matrix effect was small and the stability was good. The trough concentrations of voriconazole of 48 samples ranged from 0.4 to 11.0 μg/ml, greatly affected by liver and kidney function. The trough concentrations of posaconazole of 11 samples ranged from 0.31 to 4.58 μg/ml, dialysis may affect its drug concentration. The trough concentrations of amphotericin B of 3 samples were 47.65 μg/ml, 6.58 μg/ml and 3.84 μg/ml respectively, with significant individual differences. Conclusions The established method has high precision and accuracy, high extraction recovery and small matrix effect, and can meet the high-throughput determination of the three drugs.
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Received: 12 July 2024
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2024, Vol. 35 
