UPLC-MS/MS法检测定量干血斑中三种抗真菌药物  

Quantification of three antifungal drugs in dry blood spots by UPLC-MS/MS

作　　者：厉圣斌 刘博宇[2] 姚婉清 罗盼超 谢义政 黄欣欣 袁晶华 蔡增轩[3] 陈启 LI Sheng-bin;LIU Bo-yu;YAO Wan-qing;LUO Pan-chao;XIE Yi-zheng;HUANG Xin-xin;YUAN Jing-hua;CAI Zeng-xuan;CHEN Qi(Zhejiang Shuren University,Hangzhou 310015;Peking University People’s Hospital,Beijing 100044;Zhejiang Provincial Center for Disease Control and Prevention,Hangzhou 310051)

机构地区：[1]浙江树人学院,杭州310015 [2]北京大学人民医院,北京100044 [3]浙江省疾病预防控制中心,杭州310051

出　　处：《中南药学》2024年第11期3021-3025,共5页Central South Pharmacy

基　　金：浙江省基础公益研究计划(No.LTGC23H200001);浙江省大学生科技创新活动计划(No.2022R421A032)。

摘　　要：目的建立一种基于液相色谱串联四极杆质谱联用法同时检测定量干血斑中伏立康唑、泊沙康唑、艾沙康唑的方法。方法将含有10μL末梢血的干血斑完整转移至试管中,经含有同位素内标的70%乙腈水溶液萃取,采用C18反相色谱柱作为固定相,含0.1%甲酸的超纯水和甲醇作为流动相进行色谱分离,采用电喷雾正离子电离,在多反应监测模式下进行检测。结果伏立康唑、泊沙康唑在0.050~2.5μg·mL-1内,艾沙康唑在0.10~5.0μg·mL^(-1)内与测定值线性关系良好,线性相关系数(r)均大于0.99;各浓度的批内与批间精密度RSD<5.3%,提取回收率为92.1%~104.3%;伏立康唑和泊沙康唑的检测限均为0.050μg·mL^(-1),艾沙康唑的检测限为0.10μg·mL^(-1);在45℃极端环境保存7 d的条件下稳定。结论该方法可同时对三种抗真菌药物进行准确、精密的定量检测;干血斑样本稳定性好,能够在非温控条件下采用普通快递进行运输,适用于远程医疗中的样本采集和运输,有效降低医疗成本,提高药学服务的可及性。Objective To simultaneously quantify voriconazole,posaconazole,and isavuconazole in dry blood spots with liquid chromatography-tandem triple quadrupole mass spectrometry(UPLCMS/MS).Methods Dry blood spots of 10μL capillary blood were transferred intactly to tubes and extracted with 70% acetonitrile water solution containing isotopic internal standards.Chromatographic separation conducted on C18 reversed-phase column with 0.1% formic acid in water and methanol as the mobile phase.Performed with positive electrospray ionization in multiple reaction monitoring mode was used in the detection.Results Voriconazole and posaconazole at 0.050~2.5μg·mL^(-1),and isavuconazole at 0.10~5.0μg·mL^(-1) showed good linearity(correlation coefficients r>0.99).The intra-batch and inter-batch precision RSD at all concentrations<5.3%,and spiked recoveries ranged from 92.1% to 104.3%.The limits of detection were all 0.050μg·mL^(-1) for voriconazole and posaconazole,and 0.10μg·mL^(-1) for isavuconazole.The analytes were stable under extreme conditions at 45℃ for 7 days.Conclusion The three antifungal drugs are quantified with high accuracy and precision with the present method.Dry blood spot samples are stable,allowing for fast transportation without temperature-controlled.It is feasible for remote sample collection and transportation,this reducing healthcare cost and improving the accessibility of pharmaceutical service.

关 键 词：定量干血斑 液相色谱串联质谱法 治疗药物浓度监测 伏立康唑 泊沙康唑 艾沙康唑 

分 类 号：R927[医药卫生—药学] R284.1