Although pure α-mangostin has shown a variety of pharmacological activities in in vitro assays at present it is uncertain if the same magnitude of effects will be achieved in vivo when its low bioavailability is considered.

The xanthones α-mangostin and γ-mangostin are the major bioactive compounds in Garcinia mangostana (mangosteen) fruit extracts. Previously, we reported the pharmacokinetic properties of α-mangostin in rats. The purpose of this follow-up study was to compare the pharmacokinetic characteristics of α-mangostin and γ-mangostin in rats if administered as either a pure compound or as a component of a mangosteen fruit extract. The absolute bioavailability of γ-mangostin when administered as a pure compound was determined by giving male Sprague Dawley rats 2 mg/kg γ-mangostin intravenously or 20 mg/kg orally. A 160 mg/kg aliquot of mangosteen fruit extract was administered, containing α- and γ-mangostin doses equal to 20 mg/kg and 4.5 mg/kg of each pure compound, respectively. Plasma samples were collected for both pharmacokinetic studies, and compound concentrations were measured by LC-MS/MS. The pharmacokinetic of γ-mangostin after intravenous administration followed a two-compartment body model. The half-life of the distribution phase was 2.40 min, and that of the elimination phase was 1.52 h. After oral administration, both α- and γ-mangostin underwent intensive first-pass metabolism, and both compounds were conjugated rapidly after oral administration. When given as an extract, the total absorption of α- and γ-mangostin was not increased, but the conjugation was slower, resulting in increased free (unconjugated) compound exposure when compared to pure compound administration. Since reported beneficial biological activities of mangosteen xanthones are based on the free, unconjugated compounds, food supplements containing mangosteen fruit extracts should be preferred over the administration of pure xanthones.

A rapid and selective high-throughput HESI-LC-MS/MS method for determining eight cytochrome P450 probe drugs in one-step extraction and single run was developed and validated. The four specific probe substrates midazolam, dextromethorphan, tolbutamide, theophylline and their metabolites 1-hydroxymidazolam, dextrorphan, hydroxyl(methyl)tolbutamide, 1,3-dimethyluric acid, together with the deuterated internal standards, were extracted from rat plasma using a novel 96-well Hybrid-SPE™-precipitation technique. The bioanalytical assay was based on reversed phase liquid chromatography coupled with tandem mass spectrometry in the positive ion mode using selected reaction monitoring for drug (-metabolite) quantification. All analytes were separated simultaneously in a single run that lasted less than 11 min. The intra- and inter-day precisions for all eight substrates/metabolites were 1.62-12.81% and 2.09-13.02%, respectively, and the relative errors (accuracy) for the eight compounds ranged from -9.62% to 7.48% and -13.84% to 8.82%. Hence, the present method provides a robust, fast and reproducible analytical tool for the evaluation of four major drug metabolising cytochrome P450 (3A4, 2C9, 1A2 and 2D6) activities with a cocktail approach in rats to clarify herb-drug interactions. The method can be used as a basic common validated high-throughput analytical assay for in vivo interaction studies.

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