中国医院用药评价与分析2025，Vol.25Issue(4)：430-433,437,5.DOI:10.14009/j.issn.1672-2124.2025.04.011
二维液相色谱法测定贝达喹啉血药浓度方法学的建立与临床应用
Establishment and Clinical Application of Two-Dimensional Liquid Chromatography for Determination of Blood Concentration of Bedaquiline
摘要
Abstract
OBJECTIVE:To provide feasible technical support for clinical therapeutic drug monitoring of bedaquiline.METHODS:(1)One-dimensional liquid chromatography,the one-dimensional column was Aston SX1(3.5 mm×25.0 mm,5.0 μm),the mobile phase was acetonitrile-methanol-40 mmol/L phosphoric acid aqueous solution(V∶V∶V=3∶1∶4),the pH was adjusted by diethylamine to be 7.0,with the flow rate of 1.0 mL/min.(2)Two-dimensional liquid chromatography,the two-dimensional column was Aston SCB(4.6 mm×100.0 mm,5.0 μm),the mobile phase was acetonitrile-isopropanol-45 mmol/L phosphoric acid aqueous solution(V∶V∶V=7∶1∶5),the pH was adjusted by diethylamine to be 5.8,with the flow rate of 1.2 mL/min.(3)The intermediate column was Aston SCB(4.6 mm×10.0 mm,3.5 μm),the auxiliary mobile phase was pure water,with the flow rate of 0.01 mL/min.The detection wavelength was 235 nm/225 nm,the column temperature was 40℃with injection volume of 200 μL.RESULTS:The concentration of bedaquiline and metabolite N-monomethyl metabolite(M2)were respectively ranged from 0.233 to 10.494 μg/mL and 0.236 to 10.640 μg/mL,which showed a good linear correlation with the peak area,and the regression equation was Y=(2.913 94×106)X-21 600.2(R=0.999 8).The lower limits of quantification of bedaquiline and M2 were respectively 0.233 and 0.236 μg/mL,and the limits of detection were respectively 0.046 and 0.047 μg/mL.Results of intra-batch and inter-batch precision investigations showed that the RSD of bedaquiline and M2 were both<3%.Results of accuracy investigation showed that the deviation of the measured concentration from the theoretical concentration of bedaquiline was in the range of 93.42%to 104.06%,and that of M2 was in the range of 95.86%to 101.27%.Results of stability investigation showed that the RSD of bedaquiline and M2 under different conditions were both<3.00%.The extraction recovery rates of bedaquiline and M2 were respectively 98.01%to 98.56%and 98.64%to 99.01%,the transfer recovery rates were respectively 95.22%and 99.00%.CONCLUSIONS:The determination method for blood concentrations of bedaquiline and M2 based on two-dimensional liquid chromatography has the characteristics of high sensitivity,good reproducibility,high automation and simple sample pretreatment,which meets the demand of plasma sample detection,provides new and practical means of efficacy monitoring for clinical patient treatment,and technical support for reducing the occurrence of resistance to the new anti-tuberculosis drug bedaquiline.关键词
二维液相色谱法/贝达喹啉/N-单甲基代谢物/血药浓度/方法学/临床应用Key words
Two-dimensional liquid chromatography/Bedaquiline/N-monomethyl metabolite/Blood concen-tration/Methodology/Clinical application分类
医药卫生引用本文复制引用
普琳梅,汪习成,刘恒丽,王峰,宋贤..二维液相色谱法测定贝达喹啉血药浓度方法学的建立与临床应用[J].中国医院用药评价与分析,2025,25(4):430-433,437,5.基金项目
云南省教育厅科学研究基金项目(No.2024JO317) （No.2024JO317）
