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Drug Metabolism and Disposition Fast Forward
First published on May 21, 2009; DOI: 10.1124/dmd.109.028019

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Received for publication April 15, 2009.
Revised May 15, 2009.
Accepted for publication May 19, 2009.

Metabolite Profiling of Hydroxycinnamate Derivatives in Plasma and Urine Following the Ingestion of Coffee by Humans: Identification of Biomarkers of Coffee Consumption

Angelique Stalmach 1, William Mullen 1, Denis Barron 2, Kenichi Uchida 3, Takao Yokota 3, Christophe Cavin 2, Heike Steiling 2, Gary Williamson 2, Alan Crozier 1*

1 University of Glasgow 2 Nestle Research Center 3 Teikyo University

* Address correspondence to: E-mail: a.crozier{at}bio.gla.ac.uk

Abstract

Human subjects drank coffee containing 412 µmol of chlorogenic acids and plasma and urine were collected 0-24 h after ingestion and were analyzed by HPLC-PDA-MSn. Within 1 h, some of the components in the coffee reached low nM peak plasma concentrations (Cmax) while chlorogenic acid metabolites, including caffeic acid-3-O-sulfate and ferulic acid-4-O-sulfate, and sulfates of 3- and 4-O-caffeoylquinic acid lactones, had higher Cmax values. The short time to reach Cmax (Tmax) indicates absorption of these compounds in the small intestine. In contrast, dihydroferulic acid, its 4-O-sulfate and dihydrocaffeic acid-3-O-sulfate exhibited much higher Cmax values (145-385 nM) with Tmax values in excess of 4 h, indicating absorption in the large intestine and the probable involvement of catabolism by colonic bacteria. These three compounds, along with ferulic acid-4-O-sulfate and dihydroferulic acid-4-O-glucuronide, were also major components to be excreted in urine (8.4 - 37.1 µmol) after coffee intake. Feruloylglycine, which is not detected in plasma, was also a major urinary component (20.7 µmol excreted). Other compounds, not accumulating in plasma but excreted in smaller quantities, included the 3-O-sulfate and 3-O-glucuronide of isoferulic acid, dihydro(iso)ferulic acid-3-O-glucuronide and dihydrocaffeic acid-3-O-glucuronide. Overall, the 119.9 µ;mol excretion of the chlorogenic acid metabolites corresponded to 29.1% of intake, indicating that as well as being subject to extensive metabolism, chlorogenic acids in coffee are well absorbed. Pathways for the formation of the various metabolites with in the body are proposed. Urinary dihydrocaffeic acid-3-O-sulfate and feruloylglycine are potentially very sensitive biomarkers for the consumption of relatively small amounts of coffee.


Key words: absorption, bioavailability, glucuronidation, mass spectrometry, metabolite identification, metabolite kinetics, methylation, oral absorption, pharmacokinetics, sulfate conjugation




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