Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
School of Chemistry and Biology, Yichun College, Yichun City, Jiangxi Province 336000, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Dec 1;1102-1103:17-22. doi: 10.1016/j.jchromb.2018.10.016. Epub 2018 Oct 18.
Alpha-fluoro-beta-alanine (FBAL), the final metabolite of capecitabine, is a toxic compound excreting with urine. Magnesium isoglycyrrhizinate injection is a traditional Chinese medicine prescribed with capecitabine as a hepatoprotective agent. The purposes of this study are to develop an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for direct, efficient and sensitive determination of FBAL in urine and explore the influence of magnesium isoglycyrrhizinate on the excretion of FBAL in rat model. The method development and validation were successfully achieved. The run time was 3 min based on an HILIC column and linear range was 0.02-10.00 μg/mL. The mass detection was completed using electrospray ionization in positive ionization mode with a multiple reaction monitoring mode. A simplified sample pretreatment procedure was performed by direct dilution using 50% acetonitrile aqueous solution with the matrix effect range 48.98%-52.10% and the recovery range 78.68%-83.28%. The intra-day and inter-day precision and accuracy were <11% and within ±6%, and the stability, specificity, carry-over, dilution effect and linearity all conformed to the criterions. This study presented preliminary results that the influence of magnesium isoglycyrrhizinate on the excretion of FBAL was insignificant in rats based on this new developed method.
氟代-β-丙氨酸（FBAL）是卡培他滨的终末代谢产物，是随尿液排出的有毒化合物。异甘草酸镁注射液是一种与卡培他滨联合使用的中药，具有肝保护作用。本研究旨在建立一种超高效液相色谱串联质谱（UHPLC-MS/MS）法，直接、高效、灵敏地测定尿液中的 FBAL，并探讨异甘草酸镁对 FBAL 在大鼠模型中排泄的影响。该方法的开发和验证取得了成功。基于 HILIC 柱，运行时间为 3 分钟，线性范围为 0.02-10.00μg/mL。采用电喷雾正离子模式，以多反应监测模式进行质量检测。采用 50%乙腈水溶液直接稀释的简化样品预处理方法，基质效应范围为 48.98%-52.10%，回收率范围为 78.68%-83.28%。日内和日间精密度和准确度均<11%，且在±6%范围内，稳定性、特异性、残留、稀释效应和线性均符合标准。本研究初步结果表明，基于新建立的方法，异甘草酸镁对 FBAL 排泄的影响在大鼠中并不显著。
