Quantification of 3‐bromopyruvate in rat plasma by HPLC–MS/MS employing precolumn derivatization and the application to a pharmacokinetics study
Quantification of 3‐bromopyruvate in rat plasma by HPLC–MS/MS employing precolumn derivatization and the application to a pharmacokinetics study
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采用柱前衍生化的 HPLC-MS/MS 定量大鼠血浆中的 3-溴丙酮酸及其在药代动力学研究中的应用
DOI：
10.1002/bmc.5477
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发表时间：
2022
影响因子：
1.8
通讯作者：
Sun Yongbing
中科院分区：
文献类型：
--
作者：
Liu Hui;Zhang Qi;Huang Hesong;Lvjiang Hu;Zhao Xiaojuan;Xu Chuanxi;Wang Zhiqiang;Zhang Chenlei;Qiu Mingliang;Zhan Yang;Sun Yongbing
本文首次建立了测定大鼠血浆中3-溴丙酮酸(3-BrPA)的高效液相色谱-串联质谱法(HPLC-MS/MS)。色谱柱为C18色谱柱(10 0×2.1 mm，1.7μm)，电喷雾电离源的三重四极杆质谱仪进行检测。采用蛋白质沉淀法从大鼠血浆中提取3-BrPA，再用4-硝基-1，2-苯二胺衍生化，得到质谱图。根据美国食品和药物管理局的指导，该方法得到了充分的验证。3-BrPA的浓度在0.5~1,000.0 ng/ml范围内呈良好的线性关系。精密度、准确度、萃取回收率、基质效应均在可接受范围内。3-BrPA和3-BrPA-L-Val-L-Ile(3-BrPA，3-BrPA-L-Valine-L-异亮氨酸的二肽前体药物)分别给SD大鼠后，该方法被用于支持药代动力学研究。
A simple high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method has been developed for the determination of 3-bromopyruvate (3-BrPA) in rat plasma for the first time. The analytes were separated on a C18 column (100 × 2.1 mm, 1.7 μm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. 3-BrPA was extracted from rat plasma with protein precipitation, and then derivatized with 4-nitro-1,2-phenylenediamine to obtain the mass signal because 3-BrPA could not be detected in mass spectrometry. The method was fully validated according to the US Food and Drug Administration guidance. The method was linear over the concentration range 0.5–1,000.0 ng/ml for 3-BrPA. The precision and accuracy, extraction recovery, and matrix effect were within acceptable limits. The method was then applied to support a pharmacokinetic study after 3-BrPA and 3-BrPA-l-Val-l-Ile (a dipeptide prodrug of 3-BrPA, 3-BrPA-l-Valine-l-isoleucine) had been administered to the Sprague–Dawley rats, respectively.