摘要
目的:建立贝达喹啉人体血药浓度的测定方法并应用。方法:血浆样本以舍曲林为内标经甲醇沉淀蛋白后,采用C18色谱柱甲醇^(-1)0 mmol·L^(-1)甲酸铵溶液梯度洗脱分离,电喷雾正离化,多反应监测模式(MRM)定量测定贝达喹啉和舍曲林的离子反应分别为m/z 555.2→229.0和m/z 306.2→159.0。结果:贝达喹啉检测质量浓度的线性范围为0.010~3.0μg·mL^(-1)(r=0.9995),定量下限为0.010μg·mL^(-1);方法经验证符合生物样本分析要求。用于6例耐多药结核病(MDR-TB)患者贝达喹啉治疗血药浓度监测,患者在治疗第7天血浆中贝达喹啉血药峰浓度Cmax为(3.48±0.70)μg·mL^(-1),峰时间tmax为(5.33±1.03)h,半衰期t1/2为(18.73±6.39)h;血药浓度曲线下面积AUClast为(50.16±9.74)μg·h·mL^(-1),平均驻留时间MRT为(10.62±0.69)h;其中CL/F为(4.83±1.34)L·h^(-1),V/F为(123.55±24.19)L。结论:所建LC-MS/MS法专属性好,准确度高,精密度与灵敏度均较好,可用于MDR-TB患者体内贝达喹啉血药浓度的检测。
Objective:To establish a method and apply it for the determination of plasma bedaquiline concentrations.Methods:Human plasma samples containing bedaquiline were spiked with sertraline as an internal standard.After protein precipitation with methanol,the samples were subjected to separation using a C18 chromatographic column with a gradient elution of methanol and 10 mmol·L^(-1)ammonium formate solution.Detection was performed using electrospray ionization,and multiple reaction monitoring(MRM)was employed for the quantitative determination of bedaquiline and sertraline,with ion transitions at m/z 555.2→229.0 and m/z 306.2→159.0,respectively.Results:The linear range for the determination of bedaquiline was found to be 0.010 to 3.0μg·mL^(-1)(r=0.9995),with a quantification limit of 0.010μg·mL^(-1).The validated method conformed to the requirements for analysis of biological samples.For the monitoring of bedaquiline blood concentrations during treatment in six multidrug-resistant tuberculosis(MDR-TB)patients,the peak plasma concentration(Cmax)of bedaquiline on the 7th day of treatment was(3.48±0.70)μg·mL^(-1),with a time to peak concentration(tmax)of(5.33±1.03)hours,and a half-life(t1/2)of(18.73±6.39)hours.The area under the concentration-time curve(AUClast)was 50.16±9.74μg·h·mL^(-1),and the mean residence time(MRT)was(10.62±0.69)hours.The apparent clearance(CL/F)was(4.83±1.34)L·h^(-1),and the apparent volume of distribution(V/F)was(123.55±24.19)L.Conclusions:The established LC-MS/MS analysis method has good specificity,high sensitivity,accuracy and precision,and can be used to determine bedaquiline plasma concentrations in MDR-TB patients.
作者
王仲建
陈夏霖
张侠
张向荣
曹辉
王允吉
WANG Zhongjian;CHEN Xialin;ZHANG Xia;ZHANG Xiangrong;CAO Hui;WANG Yunji(Department of Pharmacy,the Second Hospital of Nanjing,Afiliated to Nanjing University of Chinese Medicine,Nanjing 210003,China;Department of Tuberculosis,the Second Hospital of Nanjing,Affiliated to Nanjing University of Chinese Medicine,Nanjing 210003,China;Jiangsu Kanion Pharmaceutical Co.,Ltd.,Nanjing 211112,China)
出处
《药学与临床研究》
2024年第1期20-25,共6页
Pharmaceutical and Clinical Research
基金
国家“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十三五”项目(2018ZX10725509)
江苏省教育厅省高校自然科学基金面上项目(21KJB350024)。
