Pharmacokinetics and excretion study of sophoricoside and its metabolite in rats by liquid chromatography tandem mass spectrometry

• Evaluate the pharmacokinetic profiles of sophoricoside and its metabolite.
• Excretion studies of sophoricoside and its metabolite in bile, urine and feces.
• Assay of sophoricoside and its metabolite after oral administration of sophoricoside.
• Determination of sophoricoside and its metabolite genistein by LC–MS.
• There were double peaks of genistein in rat plasma.

In this study, a new liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the determination of sophoricoside and its metabolite genistein in rat plasma, bile, urine and feces after oral administration of sophoricoside, using sulfamethalazole as internal standard (IS). The separation was performed on a reverse phase C18 column with gradient elution consisting of 0.2‰ aqueous formic acid and methanol (containing 0.2‰ formic acid). The detection was accomplished by multiple-reaction monitoring (MRM) scanning after electrospray ionization (ESI) source operating in the negative ionization mode. The optimized mass transition ion pairs (m/z) for quantitation were 431.2/268.2 for sophoricoside, 268.7/133.0 for genistein and 252.0/156.0 for IS. This developed method provides good linearity (r > 0.9983), intra- and inter-day precisions (RSD < 8.31%) with accuracies (RE, −6.91 to 6.66%), stability (RE, −7.45 to 6.59%), extract recovery (76.24 to 93.30%) and matrix effect (81.06–106.2%) of the analytes in plasma, bile, urine and feces. The mean elimination half-life (t1/2) of sophoricoside and genistein were 59.78 ± 7.19 and 103.14 ± 16.97 min, respectively. The results showed that sophoricoside was rapidly absorbed and then eliminated from rat plasma. The total recoveries of sophoricoside in bile, urine and feces were about 0.0111%, 1.76% and 11.13%. The amounts excreted of genistein were 0.42 ± 0.02 μg in bile, 10.15 ± 0.22 μg in urine and 2.92 ± 0.13 μg in feces. This is the first report to evaluate the pharmacokinetics and excretion of sophoricoside and its metabolite in rats after oral administration of sophoricoside monomer. The results provided a meaningful basis for the clinical application of sophoricoside.