液质联用方法测定抗真菌药物伏立康唑、泊沙康唑及两性霉素B的药物浓度OACSTPCD

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 col-umn(4.6 mm×50 mm,2.7 μm).The mobile phase was methanol/0.2%acetic acid solution,with gradient elution.The mass spec-trometry was carried out using an electrospray ion source,multiple reaction monitoring(MRM),and positive ion mode.Acetamino-phen 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 in-jection analysis,with an injection volume of 5 μl.The analysis time was 9.0 minutes.Results There was no interference to the deter-mination of endogenous substances in the samples,and the three drugs had good linear relationships within their respective linear ran-ges,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 con-centration.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.