The aim was to study the elimination and Phase 2 biotransformation of 4'-hydroxy-4-methoxychalcone (1) and its bis-Mannich analog (2) in the small intestine of the rat.


Earlier studies indicated that chalcones are promising starting points for drug design. Aminomethylation of drugs is considered to improve their delivery into the human body.


To set up validated HPLC-UV methods to quantitate the investigated chalcones in the rat intestinal perfusates. Comparison of intestinal disappearance and Phase 2 metabolic profile of the 4’-hydroxychalcone (1) and a bis-Mannich analog (2).


Chalcones 1 and 2 were luminally perfused in the small intestine of rats at a concentration of 240 μM and 280 μM, respectively. Analysis of the collected intestinal perfusate samples was performed by a validated HPLC-UV method. Using HPLC-MS, the samples were analyzed for Phase 2 metabolites as well.


Elimination kinetics of the two 4’-hydroxychalcones displayed characteristic differences having the nonpolar chalcone 1 higher elimination rate over the 90-minute ex vivo experiments. HPLC-MS analysis of the perfusates indicated the presence of glucuronide, sulfate, and glutathione conjugates in the parent molecules. Intestinal disappearance and sulfation of the bis-Mannich derivative 2 showed characteristic differences compared to 1


The results demonstrate, to the best of our knowledge, for the first time, how the title structural modification of phenolic chalcones affects intestinal elimination and Phase 2 metabolism of the compounds


Study on ex vivo intestinal elimination of a 4'-hydroxy-4-methoxychalcone and its bis-Mannich analog.

Development of validated HPLC-UV methods for quantitation of 4’-hydroxychalcone derivatives in rat intestinal perfusates.

HPLC-MS identification of Phase 2 metabolites of 4’-hydroxychalcones in rat intestinal perfusates.

Keywords: Hydroxychalcones, Mannich bases, HPLC, HPLC-MS, Intestinal absorption, Intestinal metabolism.
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