LC‐MS/MS methods for the determination of edaravone and/or taurine in rat plasma and its application to a pharmacokinetic study

Abstract

Three liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3-methyl-1-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid-methanol, isocratic 0.1% formic acid-methanol (90:10) and 0.02% formic acid-methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H](+) 175.1 → 133.0 and [M + H](+) 189.2 → 147.0 for edaravone and its IS, m/z [M - H](-) 124.1 → 80.0 and [M - H](-) 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co-administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration-time curve, mean residence time, half-life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible.

Two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to study the excretion and metabolic interaction of edaravone and taurine in rats

“…Referring to previous study [12,18,19], good responses were obtained in positive ionization mode for edaravone and its IS, and negative ionization mode for taurine and its IS. Fig.…”

“…For recognizing the pharmacokinetic interaction and exploring the potential possibility of new drug containing edaravone and taurine, non-clinical pharmacokinetic study of combination of two drugs is essential, which is the basis of their pharmacodynamic and toxicology. Recently, pharmacokinetic interaction of taurine co-administrated with edaravone in rat plasma has been reported by our group [12]. However, there is presently no available literature which describes excretion and metabolism interaction of taurine co-administrated with edaravone.…”

“…Our group [12,19] column was respectively selected to separate taurine or edaravone. In the HILIC mode, acetonitrile was the weak solvent and water was the strong solvent.…”

“…The latter justly focused on the determination of edaravone in plasma, which was also been proven by our group to be not available for the determination of bile, feces and urine. When simultaneous LC-MS/MS determinations of edaravone and taurine was performed referring to our previous work [12,19], heavy interference and matrix effect from bile, feces and urine happed, which was difficult to be resolved by optimizing chromatographic condition and sample process after lots of experiments in our laboratory.…”

Stress degradation of edaravone: Separation, isolation and characterization of major degradation products

“…Some methods have already been reported in the literature for estimation of EDA; these include fluorescent assay (Liao, Yan, Xu, & Sun, ), UV spectrophotometry (Patel, Raj, & Jain, ), HPTLC (Gandhimathi, Kumar, Baghla, & Ravi, ), HPLC (Fanse & Rajput, ; Patel et al, ; Zhen, Wei, Li, Ping, & Zhogao, ) and LC‐MS/MS (Tang et al, ; Yao, Hang, Wang, Cai, & Huang, ). Recently we have developed a QbD‐assisted TLC‐densitometry method of EDA (Baghel & Rajput, ).…”