Pharmacokinetics of Hydroxytyrosol and Its Sulfate and Glucuronide Metabolites after the Oral Administration of Table Olives to Sprague-Dawley Rats.

The pharmacokinetics (PK) of hydroxytyrosol and its metabolites were characterized following oral administration to Sprague-Dawley rats of 3.85 and 7.70 g of destoned Arbequina table olives/kg. Plasma samples were analyzed using a fully validated method consisting of liquid extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Noncompartmental PK analysis of hydroxytyrosol demonstrated linear PK between doses of 2.95 and 5.85 mg hydroxytyrosol/kg. Half-life was approximately 2.5 h, while mean residence time was around 4 h. Clearance occurred by conversion to two sulfate and two glucuronide conjugates. The area under the plasma concentration-time curve (AUC) ratios of metabolites versus parent hydroxytyrosol was approximately 7-9-fold for the sulfate and below 0.25 for the glucuronide, indicating sulfation as the predominant metabolic pathway. Despite extensive metabolism, hydroxytyrosol remained in plasma for up to 8 h with AUCs of 4293 and 8919 min·nmol/L for the doses of 3.85 and 7.70 g/kg, respectively. Therefore, table olives provide a more sustained plasma profile than other foods containing hydroxytyrosol, which may enhance its health-protecting activities.

Simultaneous Determination of Phenolic Compounds in Plasma by LC-ESI-MS/MS and Their Bioavailability after the Ingestion of Table Olives.

The role attributed to polyphenols on human health needs to be correlated with their plasmatic concentrations after food consumption. Then, a method based on liquid-liquid extraction followed by highly sensitive LC-ESI-MS/MS analysis was developed to determinate 16 phenolic compounds in plasma. Validation gave appropriate recovery, matrix effect (80%-120%), linear correlation (R2 > 0.995), precision (<15%), LOQ (0.04-2.51 nM), and short chromatographic run. The method was verified after the administration of Arbequina table olives to rats. A single dose of destoned olives was given by gavage, and plasmatic concentrations of polyphenols were analyzed at 30 min. Interestingly, the profile found in plasma greatly differed from that of the olives. Plasmatic concentrations, from highest to lowest, were salidroside, p-coumaric acid, hydroxytyrosol, verbascoside, tyrosol, luteolin, and luteolin-7-O-glucoside. In conclusion, a simple and robust method was developed, enabling the identification and quantification of unaltered polyphenols in plasma after olives consumption, thus demonstrating its suitability for pharmacokinetics studies.