Plasma pharmacokinetics and brain distribution kinetics of lapachol in rats using LC-MS and microdialysis techniques

The objective of this paper was to investigate the plasma pharmacokinetics and brain distribution kinetics of lapachol in rats. A sensitive and specific high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of the bioactive naphthoquinone lapachol in rat plasma and brain dialysates after oral administration. The analytes were determined using the negative electrospray ionization mode in multiple reaction monitoring (MRM). The chromatographic separation was on a ZORBAX SB-C18 column coupled with a C18 guard column using a mobile phase composed of acetonitrile–water containing 0.1% formic acid at a flow rate of 0.5 mL min−1. The methods were sensitive with good linearity and no endogenous material interferences. The inter- and intra-day precision and accuracy of lapachol in plasma and the brain were lower than 12%. The methods were successfully applied to the quantification and pharmacokinetic study of lapachol in rats. The results indicated that the disposition profile of lapachol fitted to first order elimination and the two-compartment open model. Lapachol could pass through the blood brain barrier and went through enterohepatic circulation in rats with extending in vivo exposure time after oral administration. In summary, these findings provide an important pharmacological foundation for developing a novel drug and the clinical use of lapachol.