The use of stable isotopes in drug metabolism studies.
The use of stable isotopes in drug metabolism studies.
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DOI：
10.1053/sper.2001.24568
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发表时间：
2001-06
影响因子：
3.4
通讯作者：
F. Abramson
中科院分区：
文献类型：
--
作者：
F. Abramson
尽管稳定同位素在药物代谢研究中的使用有着悠久的历史，但在安全性放在首位的妊娠药物研究中对其进行评估是合适的。通过大量人类和动物实验已经证实，稳定同位素本身很少产生除其所附着的分子之外的额外毒性。对于代谢研究中涉及的稳定同位素的分析，质谱法起着主导作用。现在存在几种基于质谱的技术，能够选择性定量检测稳定同位素，与 14C 在线放射性监测仪相比，具有更高的灵敏度和更好的色谱分辨率保留。甚至质量平衡研究也可以使用稳定同位素进行，这是一种仍然主要使用放射性同位素的实验。稳定同位素使用的一些最新进展涉及生物聚合物，其中可以从在同位素标记的生长培养基中生长的细胞产生完全同位素标记的物质。稳定同位素显示出安全性、敏感性、特异性和多功能性，应该在妊娠期药物代谢研究中发挥重要作用。
Although there is a long history of stable isotopes use in drug metabolism research, it is appropriate to evaluate them in pregnancy drug studies in which safety takes highest priority. It is well established through a number of human and animal experiments that stable isotopes themselves rarely generate additional toxicities beyond the molecules to which they are attached. For the analysis of stable isotopes involved in metabolism studies, mass spectrometry plays the predominant role. Several mass spectrometry-based techniques now exist that enable the selective quantitative detection of stable isotopes with better sensitivity and better retention of chromatographic resolution than do in-line radioactivity monitors for 14C. Even mass balance studies can be performed by using stable isotopes, a type of experiment that still predominantly uses radioisotopes. Some of the newest developments in the use of stable isotopes involve biopolymers, in which fully isotope-labeled species can be generated from cells grown in isotopically labeled growth media. Having shown safety, sensitivity, specificity, and versatility, stable isotopes should play an important role in drug metabolism studies in pregnancy.