Metabolic profile of curcumin self‐emulsifying drug delivery system in rats determined by ultra‐high performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry

Abstract

Curcumin (Cur) is a natural anticancer pigment, but its poor absorption and extensive metabolism limit its clinical applications. In this study, an ultra‐high performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry method was employed to investigate the metabolic profiles of a Cur self‐emulsifying drug delivery system (C‐SEDDS) in rat plasma, urine, bile and feces after oral administration at 100 mg/kg. Protein precipitation, solid‐phase and ultrasonic extractions were used to prepare different biosamples. A total of 34 metabolites were identified using available reference standards, or tentatively identified based on the mass spectrometric fragmentation patterns and the chromatographic elution order. Nine metabolites of Cur were found for the first time in vivo. Glucuronidation, sulfation, reduction, dehydroxylation, demethylation, demethoxylation and methylation were its possible metabolic reactions. Moreover, the differences were compared in terms of plasma metabolites found in C‐SEDDS‐treated, Cur suspension‐treated and rats treated with a commercial curcuminoid phospholipid complex administered at the same oral dose. Dihydrocurcumin (DHC), DHC glucuronide and methylated DHC were found only in the metabolic profile of C‐SEDDS‐treated rat plasma, suggesting that different drug delivery systems may cause a change in Cur metabolic pathways. This study provides a sensitive and rapid method for the identification of Cur metabolites in biosamples.

Lipid-Based Nanocarrier System for the Effective Delivery of Nutraceuticals

“…The incorporation of bioactives such as vitamin E and curcumin in SEDDS showed improved oral bioavailability due to their enhanced solubilization and cellular uptake [ 125 , 126 ]. Recently, Xu, et al [ 127 ] identified the variation of the curcumin metabolites of curcumin in rats after administering three different curcumin formulations, namely, SEDDS, suspension, and a commercial phospholipid complex. The authors identified 34 curcumin metabolites using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry technique (UPLC–MS).…”

“…Thus, a portion of curcumin was conjugated to glucuronide in the intestine and then reaches the portal vein and liver to form glucuronide/sulfate conjugates [ 129 ]. Although Xu, Tang, Zhang, Yang and Yuan [ 127 ] found an increase in bioavailability for rats administered with SEDDS formulation, the quantification of such curcumin metabolites for the different formulations is required to underpin the pharmacokinetic pathway of the SEDDS formulations.…”