Evaluation of pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in Sprague Dawley rats by liquid chromatography-tandem mass spectrometry

We aimed to investigate the pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in rats. An LC-tandem mass spectrometry (MS/MS) method for simultaneous determination of scopolin and scopoletin in rat biomatrices was developed and validated over a plasma and urine concentration range of 5.0-2000 ng/mL. Chromatographic separation was performed on a Hypersil GOLD C-18 column with acetonitrile and 0.1% formic acid in water as mobile phase with gradient elution. Detection was performed in the positive ionization and selected reaction monitoring mode. The intra- and inter-batch precision and accuracy, extraction recovery and matrix effect and stability of scopolin and scopoletin were well within the acceptable limits of variation. There was no gender-related difference in the pharmacokinetic profiles of scopolin. There were significant differences in total area under the concentration-time curve (AUC), time required to achieve a maximal concentration (T-max) and apparent clearance from plasma (Cl/F) of scopoletin between the male and female rats (p < .05). The bioavailability (F) of scopolin was exceptionally low. The maximal excretion rates were 7.61 mu g/h and 7.15 mu g/h for scopolin and 31.68 mu g/h and 25.58 mu g/h for scopoletin in male and female rats, respectively. The LC-MS/MS method was successfully applied to the pharmacokinetic, bioavailability and urinary excretion studies of scopolin and its metabolite scopoletin following a single administration of scopolin to rats.