摘要
目的 采用高效液相色谱-质谱/质谱联用（HPLC-MS/MS）技术检测人血浆中贝达喹啉浓度, 并对其应用效果进行评价。方法 人血浆样品经乙腈沉淀蛋白等处理后检测,液相色谱采用Agilent ZORBAX SB-C18 色谱柱（2.1mm×100mm, 3.5μm） 为分析柱,以甲醇-5mmol/L甲酸铵水溶液（含0.1% 甲酸） （85∶15, V/V） 为流动相, 质谱使用电喷雾离子源（ESI）, 以正离子多反应监测（MRM） 方式进行检测,分析时间为3min。结果 本测定方法不受血浆中内源性物质干扰, 贝达喹啉母离子和定量子离子的质荷比（m/z）为555.2→58.3,标准曲线线性范围为0.1~5.0μg/ml,方法的日内、日间精密度（相对标准偏差,RSD） 均小于10%, 准确率为97.8%~107%。用建立的方法检测了12例服用贝达喹啉的结核病患者,服药剂量为每日400mg时,贝达喹啉峰浓度为（3.17±1.14）μg/ml,谷浓度为（1.12±0.64）μg/ml;服药剂量为200mg/次,每周3次时,贝达喹啉峰浓度为（2.01±0.87）μg/ml,谷浓度为（0.65±0.30）μg/ml,48份样本血药浓度均在检测范围内（0.1~5.0μg/ml）。结论 本研究建立了抗结核新药贝达喹啉血浆中药物浓度的HPLC-MS/MS联用方法, 该方法适用于临床结核病患者血浆样品中贝达喹啉浓度的快速分析。
Objective To establish an high performance liquid chromatography-mass spectrometry/mass spectrometry （HPLC-MS/MS） method for the determination of bedaquiline in human plasma and to evaluate the application of the method.Methods The protein of plasma samples were precipitated with acetonitrile. HPLC-MS/MS was performed using an Agilent ZORBAX SB-C18 column （2.1mm×100mm, 3.5μm） as the analytical column. The mobile phase consisted of methanol-5mmol/L ammonium formate （containing 0.1% formic acid solution） （85∶15, v/v）. Electrospray ionization source （ESI） was applied and operated in the positive multiple reaction monitoring （MRM） mode. One analysis was completed within 3min.Results Chromatograms showed no endogenous interfering peaks with blank samples. The mass-to-charge ratio （m/z） of the parental ion and the quantitative ion of bedaquiline was 555.2→58.3. The linear calibration curve was obtained over the concentration on range of 0.1-5.0μg/ml. The inter- and intra-day precision （RSD） were less than 10%. The accuracy were 97.8%-107.0%. 48 plasm samples of 12 tuberculosis patients were detected using the established method. When the dosage was 400mg daily, the peak concentration of bedaquiline was （3.17±1.14）μg/ml, and the trough concentration was （1.12±0.64）μg/ml; when the dosage was 200mg per time, 3 times a week, the peak concentration of bedaquiline was （2.01±0.87）μg/ml, and the trough concentration was （0.65±0.30）μg/ml. The concentrations of bedaquiline in the 48 samples were in the range of calibration curve （0.1-5.0μg/ml）.Conclusion A HPLC-MS/MS method was established for the quick analysis and determination of bedaquiline （a new anti-tuberculosis drug） in plasma samples of tuberculosis patients.
作者
朱慧
刘忠泉
谢莉
郭少晨
王彬
付雷
陆宇
ZHU Hui;LIU Zhong-quan;XIE Li;GUO Shao-chen;WANG Bin;FU Lei;LU Yu(Department of Pharmacology,Beijing Key Laboratory of Drug Resistance Tuberculosis Research,Beijing Chest Hospital,Capital Medical University,Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China)
出处
《中国防痨杂志》
CAS
2018年第12期1319-1324,共6页
Chinese Journal of Antituberculosis
基金
抗结核药物新药临床评价技术平台建设（2017ZX09304009003）
北京市医院管理局“登峰”人才培养计划（DFL20151501）
关键词
色谱法
高压液相
串联质谱法
药代动力学
药物监测
贝达喹啉
Chromatography
high pressure liquid
Tandem mass spectrometry
Pharmacokinetics
Drug monitoring
Bedaquiline
作者简介
通信作者：陆宇，Email：luyu4876@hotmail．com
