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Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C 18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m / z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision ( RSD ) ranged from 1.1-9.0 % to 3.3-8.6%, respectively and the intra- and inter-day assay accuracy ( RE ) was between -8.2-9.7% and -10.3-9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (C max ) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC 0-t ) value was 6009.79 ± 567.30 ng/mL∙h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.

This research aims to study the metabolism and pharmacokinetics of phytoestrogen kobophenol A (1), the main active compound of Caragana sinica (Buc'hoz) Rehd. (Fabaceae), in rats. Metabolites of 1 in rats' feces were isolated and purified by multi-chromatograph techniques; three new metabolites of 1, named koboquinone A (M1), koboquinone B (M2) and koboquinone C (M3), were isolated, purified from rats' feces after they being orally administered with 1. Structure identification of the metabolites was fulfilled by spectroscopic analysis. M1 and M2 are structurally different to those natural occurring stilbene tetramers, which also have para-quinone structure. M1 also showed the activity of stimulating the proliferation of cultured osteoblasts. The pharmacokinetics of 1 in rats could be described by a two-compartmental model (P<0.05). The half-life was 0.68 h for i.v. administration and 5.78 h for oral administration. The oral bioavailability of 1 was calculated to be 2.0%; rats tissue distribution experiments show that 1 was prominently concentrated in livers. Both of the low oral bioavailability and the rapid reduction of 1 in blood indicated a suitable formulation is needed while it is developed as a new drug.