AIM To establish a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for the determination of blood drug concentrations of nirmatrelvir and ritonavir in human plasma and apply it to therapeutic drug monitoring(TDM).METHODS Plasma samples were precipitated,and the mobile phase consisted of 0.1％formic acid aqueous solution(phase A)and acetonitrile(phase B).Isocratic elution was used with a flow rate of 0.3 mL· min-1,a column temperature of 40 ℃,and an EC-C18 chromatographic column.Multiple reaction monitoring was conducted in positive ion mode.RESULTS The ion channels used for quantitative analysis were m/z 500 → 110(nirmatrelvir),m/z 721.2 →296.3(ritonavir),and m/z 614.4 → 421(internal standard remdesivir).In human plasma,nirmatrelvir showed good linearity in the range of 0.01 to 10 μg·mL-1,while ritonavir exhibited good linearity in the range of 0.01 to 2.0 μg·mL-1.The extraction recoveries were 79.56％to 89.91％for nirmatrelvir and 82.03％to 89.56％for ritonavir.The RSD values for intra-day and inter-day precision were all less than 15％,and the stability was satisfactory.The developed method was applied to measure the blood drug concentrations of 34 patients after oral administration of Paxlovid,which ranged from 1.04 to 18.0 μg· mL-1.CONCLUSION The HPLC-MS/MS method established in this study is rapid,highly sensitive,and accurate,and it can be applied to monitor the therapeutic drug concentration monitoring of CO VID-19 patients after taking Paxlovid.
关键词
色谱法,高压液相/串联质谱法/奈玛特韦/利托那韦/血药浓度
Key words
chromatography,high pressure liquid mass spectrometry/tandem mass spectrometry/nirmatrelvir/ritonavir/plasma concentration
维普
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