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Simultaneous determination of the novel anti-tumor candidate drug MDH-7 and 5-fluorouracil in rat plasma by LC-MS/MS: Application to pharmacokinetic interactions
Journal of Chromatography B ( IF 3 ) Pub Date : 2018-07-17 , DOI: 10.1016/j.jchromb.2018.07.022
Juan Li , Yu Chen , Piao Zhou , Qiqi Fan , Qingli Wang , Xiaorang Chen , Yingqian Su , Yanyan Diao , Meili Guo , Mengchen An , Hongmin Liu

MDH-7 (2,3,9-tri-O-acetyl-5,6-dideoxy-1,10-di-[N4′-pentoxycarbonyl-5′-fluoro cytosine]-4-ulose 1,4: 7,10-difuranose-4,8-pyranose) is a novel anti-tumor drug candidate. To study the pharmacokinetic interaction between MDH-7 and 5-fluorouracil (5-FU), a sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine the concentrations of MDH-7 and 5-fluorouracil (5-FU) in rat plasma. Plasma samples were prepared by simple liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Waters XBridge™ C18 column (5 μm, 2.1 mm × 150 mm) with the mobile phase of methanol and H2O (80:20, v/v). The ESI positive and negative ion switch was operated in the multiple reactions monitoring (MRM) mode. The calibration curves showed good linearity (r2 > 0.99) over the ranges of 50–8000 ng/mL for MDH-7 and 10–2000 ng/mL for 5-FU, respectively. The lower limit of quantitations (LLOQs) was 50 ng/mL (MDH-7) and 10 ng/mL (5-FU) with relative standard deviation (RSD) < 13.0%. The proposed method was successfully applied to simultaneous assessment of pharmacokinetic drug-drug interaction between MDH-7 and 5-FU in rats.



中文翻译:

LC-MS / MS同时测定大鼠血浆中新型抗肿瘤候选药物MDH-7和5-氟尿嘧啶:在药代动力学相互作用中的应用

MDH-7(2,3,9-三-O-乙酰基-5,6-二脱氧-1,10-二-[N4'-戊氧羰基-5'-氟胞嘧啶] -4-ulose 1,4:7, 10-difuranose-4,8-​​pyranose)是一种新型的抗肿瘤药物候选物。为了研究MDH-7和5-氟尿嘧啶(5-FU)之间的药代动力学相互作用,开发了一种灵敏而快速的液相色谱-串联质谱(LC-MS / MS)方法来同时测定MDH-7和5的浓度-大鼠血浆中的氟尿嘧啶(5-FU)。通过用乙酸乙酯进行简单的液-液萃取来制备血浆样品。色谱分离是在Waters XBridge™C18色谱柱(5μm,2.1 mm×150 mm)上进行的,流动相为甲醇和H 2。O(80:20,v / v)。ESI正负离子开关在多反应监测(MRM)模式下运行。校准曲线 在MDH-7的50–8000 ng / mL和5-FU的10–2000 ng / mL的范围内分别显示出良好的线性(r 2 > 0.99)。定量下限(LLOQs)为50 ng / mL(MDH-7)和10 ng / mL(5-FU),相对标准偏差(RSD)<13.0%。所提出的方法已成功地应用于同时评估MDH-7和5-FU在大鼠体内的药代动力学药物相互作用。

更新日期:2018-07-17
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