Kathrin Kahle

Simultaneous Determination of Voriconazole and Posaconazole Concentrations in Human Plasma by High-Performance Liquid Chromatography

ABSTRACT A simple, sensitive, and selective high-performance liquid chromatographic method for the simultaneous determination of voriconazole and posaconazole concentrations in human plasma was developed and validated. Quantitative recovery following liquid-liquid extraction with diethyl ether was achieved. Linearity ranged from 0.10 to 20.0 μg/ml for voriconazole and from 0.05 to 10.0 μg/ml for posaconazole. The intra- and interday coefficients of variation were less than 8.5%, and the lower limits of quantitation were <0.05 μg/ml.

Model experiments mimicking the human intestinal transit and metabolism of D-galacturonic acid and amidated pectin.

In order to study the human intestinal transit and metabolism of D-galacturonic acid and amidated pectin a number of model experiments were carried out. Both substrates were incubated under aerobic conditions at 37 degrees C using saliva (2 min) and simulated gastric juice (4 h). Under anaerobic conditions the substrates were incubated at 37 degrees C using human ileostomy and colostomy fluids, each obtained from three different donors, for 10 and for 24 h, respectively. D-Galacturonic acid, SCFA (acetic acid, propionic acid, and butyric acid), as well as methanol were analyzed photometrically after carbazole reaction, GC-flame ionization detection (GC-FID), and headspace solid-phase microextraction GC/MS (HS-SPME-GC/MS), respectively. D-Galacturonic acid and amidated pectin were found to be stable during incubations with saliva and simulated gastric juice, whereas both substrates underwent degradation in the course of human ileostomy and colostomy fluid incubations. D-Galacturonic acid was practically completely decomposed within 10 h and SCFA, with acetic acid as the major representative, were formed up to 98% of the incubated substrate in colostomy effluent. The amidated pectin was only degraded in part, revealing stable amounts of 22-35% and 3-17% in ileostomy (after 10 h) and colostomy fluid (after 24 h), respectively. SCFA were generated up to 59% of the applied amidated pectin. In parallel, 19-60% and 52-67% of the available methyl ester groups were cleaved in the course of incubations with ileostomy and colostomy fluids, respectively. The results demonstrate for the first time that D-galacturonic acid and amidated pectin are stable in human saliva and simulated gastric juice. The degradation of both compounds during incubation with ileostomy effluent is highlighted, providing evidence for a considerable metabolic potential of the small intestine.

The Metabolic Fate of Apple Polyphenols in Humans

Apples (Malus spp., Rosaceae) and their products contain significant concentrations of polyphenols, which have diverse biological activities and may have important beneficial effects on human health. The main polyphenols in apples are hydroxycinnamic acids, dihydrochalcones, flavonols, catechins and oligomeric procyanidins, although triterpenoids are also present in apple peel and anthocyanins in red apples. Human intervention studies have provided clear evidence that dietary polyphenols are at least partially absorbed following ingestion. They undergo extensive metabolism during the absorption process and subsequent distribution in the body. Hence, plasma and tissues are not generally exposed to polyphenols in their ingested form in vivo, and knowledge about their bioavailability, metabolism and concentrations in target tissues is of great importance when evaluating their biological effects and for ensuring that in vitro studies have physiological relevance. Metabolites, such as glucuronides, sulfates and methylated derivatives have been investigated in vivo. In addition, activities of colonic microbiota have been shown to generate other metabolites, including phenolic and short chain fatty acids. It has also been shown that deconjugations catalyzed by intracellular enzymes can occur during gastrointestinal absorption, thereby releasing aglycones. The present review summarizes current knowledge of the bioavailability and metabolism of apple-derived polyphenols in humans.