Accelerator mass spectrometry measurement of intracellular concentrations of active drug metabolites in human target cells in vivo.
Accelerator mass spectrometry measurement of intracellular concentrations of active drug metabolites in human target cells in vivo.
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加速器质谱法测量人体靶细胞体内活性药物代谢物的细胞内浓度。
DOI：
10.1038/clpt.2010.188
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发表时间：
2010
影响因子：
6.7
通讯作者：
Flexner,C
中科院分区：
文献类型：
--
作者：
Chen,J;Garner,RC;Lee,LS;Seymour,M;Fuchs,EJ;Hubbard,WC;Parsons,TL;Pakes,GE;Fletcher,CV;Flexner,C
加速器质谱法（AMS）是一种检测放射性标记化合物的超灵敏技术。我们向健康志愿者给予微量（100 μg）14 C标记的齐多夫定（ZDV），同时给予或不给予标准非标记剂量（300 mg）。 使用AMS和液相色谱-串联质谱法（LC/MS/MS）测量细胞内ZDV-三磷酸（ZDV-TP）浓度。AMS分析与LC/MS/MS具有良好的一致性，灵敏度高出30，000倍。在研究的剂量范围内（100 µg-300 mg），细胞内ZDV‐TP形成的动力学变化数倍。 AMS有望成为体内定量细胞内药物代谢物和其他生物介质的工具，Clinical Pharmacology & Therapeutics（2010）886，796-800。doi：10.1038/clpt.2010.188
Accelerator mass spectrometry (AMS) is an ultrasensitive technique to detect radiolabeled compounds. We administered a microdose (100 µg) of14C‐labeled zidovudine (ZDV) with or without a standard unlabeled dose (300 mg) to healthy volunteers. Intracellular ZDV‐triphosphate (ZDV‐TP) concentration was measured using AMS and liquid chromatography–tandem mass spectrometry (LC/MS/MS). AMS analysis yielded excellent concordance with LC/MS/MS and was 30,000‐fold more sensitive. The kinetics of intracellular ZDV‐TP formation changed several‐fold over the dose range studied (100 µg–300 mg). AMS holds promise as a tool for quantifying intracellular drug metabolites and other biomediatorsin vivo.Clinical Pharmacology & Therapeutics(2010)886, 796–800. doi: 10.1038/clpt.2010.188