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This paper is a report from a pharmacoscintigraphic study with an Egalet® constant-release system containing caffeine and natural abundance samarium oxide. First the formulation was tested in vitro to clarify integrity during irradiation in the nuclear reactor. Then six healthy male volunteers were enrolled into the in vivo study. The in vitro release of caffeine obeyed all the time linear zero-order kinetics. The in vivo release of radioactive Sm2O3 consisted of three consequent linear phases with different slopes. The release rate was fastest while the product was in the small intestine and slowest when the product was in the descending colon. In terms of the bioavailability of caffeine, the most important factor seemed to be the residence time in the ascending and transverse colon. A long residence time in these sections led to high AUC values for caffeine.

A validated method for the quantitation of trace levels of quercetin from human plasma to be used in pharmacokinetic and biomarker studies is presented. Quercetin conjugates were hydrolysed enzymatically, plasma proteins were removed using a Bond Elut C18 extraction column and additional interferences were removed by extracting them into a toluene–dichloromethane mixture. The HPLC system consisted of an Inertsil ODS-3 column (250×4.0 mm) and a mobile phase with 59% methanol in phosphate buffer (pH 2.4). High selectivity and a low quantitation limit (0.63 μg/l) were achieved by using electrochemical detection at a low potential. The method has excellent reproducibility: R.S.D. values of peak-heights were 2% and 7.9%, respectively, for within-day and between-day precision. The method was applied to a small scale study of quercetin pharmacokinetics and quercetin was shown to be absorbed from a 20 mg dose. No free quercetin was detected in plasma and no evidence of significant amounts of quercetin glycosides in plasma was found.

Background Naltrexone has been proven to be an effective treatment option for the treatment of alcohol dependency. In this article we introduce a reliable and simple method developed for the simultaneous determination of naltrexone and 6-β-naltrexol in human serum by using high-performance liquid chromatography (HPLC). Findings Liquid-liquid extraction with butyl acetate from basic solutions (pH 9) was chosen for extraction with nalorphine as an internal standard (IS). Analytes were back-extracted from organic solvent into perchloric acid. The acid extract was chromatographed by HPLC with a reverse-phase ODS-column and electrochemical detector. The mobile phase was a NaH2PO4-solution with acetonitrile as an organic modifier and octanesulphonic acid and tetraethylammonium hydrogen sulphate as ion-pair reagents. The recovery of the extraction method was 48% for naltrexone and 75% for 6-β-naltrexol. The limit of quantification was 5.0 ng/ml for naltrexone and 1.0 ng/ml for 6-β-naltrexol. The analysed concentrations of naltrexone differed from the theoretic concentrations by 0.7 to 2.3% and those of 6-β-naltrexol by 2.6%. The relative standard deviation of within-day assay was from 0.9 to 5.7% for naltrexone and from 0.8 to 4.2% for 6-β-naltrexol; for the between-day assay it was 5.7% and 4.2%, respectively. Conclusions Our results indicate that the developed method is suitable for determination of naltrexone and 6-β-naltrexol in human serum.