A direct, sensitive and efficient method for determination of alpha-fluoro-beta-alanine in urine: Evaluating the influence of magnesium isoglycyrrhizinate on excretion in rat model

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.

Abstract

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.

Keywords: Alpha-fluoro-beta-alanine; Excretion suppression; Magnesium isoglycyrrhizinate; Rat urine; UHPLC-MS/MS.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Limit of Detection
  • Linear Models
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Saponins / chemistry*
  • Tandem Mass Spectrometry / methods
  • Triterpenes / chemistry*
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / urine

Substances

  • 18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate
  • Saponins
  • Triterpenes
  • beta-Alanine
  • alpha-fluoro-beta-alanine