Folic acid and its metabolite codetermination for pharmacokinetics with circadian rhythms and evaluation of oral bioavailability

Objectives: Pharmacokinetics of Vitamins is still a challenge. In this study, folic acid (FA) was used as a model drug and aimed at investigating a reliable method for its detailed pharmacokinetic evaluations.

Methods: An high-performance liquid chromatography-tandem mass spectrometry method was developed and performed to determinate the FA and 5-methyltetrahydrofolic acid (5-methylTHF) simultaneously, which was applied to characterize the circadian rhythms as well as the pharmacokinetics of different preparations.

Key findings: The plasma concentration of 5-methylTHF in fasted state was twofold higher than that in fed state. The circadian rhythms were studied before the pharmacokinetics and revealed that free FA was almost undetected in blank plasma, while 5-methylTHF had a slight decrement at 12:00. Hence, the pharmacokinetics of FA was conducted and showed that the administration of FA solution resulted in enhancing bioavailability of 5-methylTHF comparing with FA raw material suspension, whereas the free FA level in plasma was similar. The mechanism could be that FA was rapidly metabolized to 5-methylTHF in intestinal epithelial cell after absorption, which revealed that intestinal metabolism would affect its bioavailability.

Conclusion: A suitable method was established considering the baseline level, circadian rhythms and intestinal metabolism to investigate the pharmacokinetics of FA for guiding the further research of Vitamins.