Pharmacokinetic profile and metabolite identification of bornyl caffeate and caffeic acid in rats by high performance liquid chromatography coupled with mass spectrometry.

Bornyl caffeate was initially discovered as a bioactive compound in medicinal plants. Despite the promising pharmacological activities including anti-tumor and antibacterial activities, the pharmacokinetics of the compound remain open. This work developed a high performance liquid chromatography-tandem mass spectrometric method for the determination of bornyl caffeate and caffeic acid (major metabolite and a main unit of bornyl caffeate) . Successful application of the method included identification of its metabolites and investigation on the drug pharmacokinetics. A total of 30 compounds were identified as the metabolites of bornyl caffeate in rats. We attributed these metabolites to phase I metabolic routes of reduction, oxidation, hydrolysis and phase II metabolic reactions of glucuronidation, sulfation, -methylation and glycine. Glucuronidation, sulfation, -methylation and reduction were the main metabolic pathways of bornyl caffeate. The method presented a linear range of 1-4000 ng mL. The pharmacokinetic profile of bornyl caffeate was found to be a three compartment open model, while caffeic acid fitted to a two compartment open model when it was administered alone or served as the main metabolite of bornyl caffeate. The time to peak concentration ( ) and the maximum plasma concentration ( ) of bornyl caffeate were 0.53 h and 409.33 ng mL. Compared with original caffeic acid, the compound displayed an increased half-life of elimination ( ), area under the concentration time curve from 0 to (AUC ) and area under the concentration time curve from 0 to ∞ (AUC), a decreased half-life of absorption ( ) and an identical . Taking together, we concluded that bornyl caffeate is able to rapidly initiate therapeutic effect and last for a relatively long time in rats; metabolic pathways of -methylation and reduction is key to interpret the mechanism and toxicity of bornyl caffeate.