3种三唑类药物血药浓度测定方法的建立  

Establishment of Blood-Concentration Determination Method of Three Triazole Drugs

作　　者：林志燕[1] 黄晓会[1] LIN Zhiyan;HUANG Xiaohui(Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China 200092)

机构地区：[1]上海交通大学医学院附属新华医院,上海200092

出　　处：《中国药业》2023年第10期63-67,共5页China Pharmaceuticals

基　　金：中国药理学会基金项目[CTDM(XM)-2018-02-002-038]。

摘　　要：目的建立同时测定人血清中3种三唑类抗真菌药物血药浓度的超高效液相色谱串联质谱(UPLC-MS/MS)法,并应用于临床的治疗药物监测。方法色谱柱为Agilent SB-C18柱(50 mm×2.1 mm,1.8μm),流动相为含0.1%甲酸的乙腈-水(梯度洗脱),流速为0.3 mL/min,柱温为40℃,进样量为2μL。电喷雾离子源(ESI),正离子多反应监测模式,伊曲康唑为内标。结果氟康唑、伏立康唑、泊沙康唑质量浓度分别在0.78125~100μg/mL、0.15625~20μg/mL、0.15625~20μg/mL(R2≥0.998)范围内与待测成分峰面积/内标峰面积线性关系良好;各质量浓度日内、日间精密度的RSD≤10.0%;提取回收率和基质效应的RSD值<15.0%。临床使用氟康唑患者38例,实测血药浓度为1.31~63.09μg/mL;伏立康唑48例,实测血药浓度为0~14.52μg/mL;泊沙康唑14例,实测血药浓度为0.17~5.52μg/mL。结论所建立的方法,每个样品分析时间短(仅需5 min),满足临床检测高通量要求。且该方法专属性强、灵敏度高、准确稳定,可用于人血清中氟康唑、伏立康唑、泊沙康唑血药浓度的同时测定及治疗药物监测。Objective To establish an ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for the simultaneous determination of blood concentration of three triazole antifungal drugs in human serum,and to apply it to therapeutic drugs monitoring in the clinic.Methods The chromatographic column was Agilent SB-C18 column(50 mm×2.1 mm,1.8μm),the mobile phase was acetonitrile containing 0.1%formic acid-water(gradient elution),the flow rate was 0.3 mL/min,the column temperature was 40℃,and the injection volume was 2μL.Electrospray ion source(ESI)was adopted with the positive-ion multiple reaction monitoring mode,and itraconazole was taken as the internal standard.Results The linear ranges of fluconazole,voriconazole and posaconazole were 0.78125-100μg/mL,0.15625-20μg/mL and 0.15625-20μg/mL(R2≥0.998).The RSD of intra-day and inter-day precision for the above three triazole drugs with different mass concentrations was not higher than 10.0%,and the RSD of extraction recovery and matrix effect was lower than 15.0%.There were 38,48 and 14 patients using fluconazole,voriconazole and posaconazole in the clinic respectively,and their blood concentration was in the range of 1.31-63.09μg/mL,0-14.52μg/mL and 0.17-5.52μg/mL respectively.Conclusion The analysis time of each sample is short(only 5 min)by this method,which meets the high-throughput requirements for clinical detection.Furthermore,the established method is specific,sensitive,accurate and stable,which can be used for the simultaneous determination of blood concentration of fluconazole,voriconazole,posaconazole in human serum and therapeutic drug monitoring.

关 键 词：氟康唑 伏立康唑 泊沙康唑 超高效液相色谱串联质谱法 治疗药物监测 

分 类 号：R969.1[医药卫生—药理学] R978.5[医药卫生—药学]