化学
色谱法
甲酸
选择性反应监测
药代动力学
三级四极质谱仪
电喷雾电离
代谢物
生物分析
高效液相色谱法
质谱法
串联质谱法
活性代谢物
药理学
生物化学
医学
作者
Jian Li,Meng Zhang,Hui Gan,Ruixia Gu,Zhuona Wu,Guifang Dou,Yue Gao
标识
DOI:10.1016/j.jpba.2019.05.020
摘要
A rapid, sensitive and reliable bioanalytical method was firstly developed and validated based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), for simultaneous quantitation of the novel radioprotective compound E0703 and its oxidative metabolite M1 in human plasma. Plasma samples were deproteinated with acetonitrile containing the internal standard IS1229 as precipitant and separated on a short CAPCELL PAK C18 IF2 column (2.0 mm × 20 mm, 2 μm) by gradient elution using acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid) with a run time of 2.5 min per sample. MS detection was carried out on a triple quadrupole mass spectrometer (Xevo TQ-S) coupled with electrospray ionization in positive multiple reaction monitoring (MRM) mode. The method was linear over the concentration ranges of 0.100-50.0 ng/mL for E0703 and 0.200-100 ng/mL for M1, with correlation coefficient (r2) values ≥0.993. A full validation of this method was performed, and all results were within acceptable limits. The novel assay was sensitive enough to monitor E0703 and M1 levels in human plasma, and was successfully applied to a clinical pharmacokinetic study of healthy Chinese subjects after a single oral administration of 30 mg E0703 tablets. In conclusion, the validated method is accurate, sensitive and high-throughput, and can be successfully implemented for subsequent clinical pharmacokinetic studies of E0703 and M1.
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