A simple LC-MS/MS method for determination of magnolol in rat blood and its application in a pharmacokinetic study.

A simple LC-MS/MS method was developed for determination and pharmacokinetic study of magnolol in rat blood. Blood sample pretreatment involved a one-step extraction with methanol of 100 µL blood. The chromatographic separation was carried out on a Agilent Zobax SB C18 column with a mobile phase consisting of acetonitrile-0.2% formic acid (55:45, v/v) at a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via electro spray ionization source with positive mode. A high throughput was achieved with a run time of 4 min per sample. The standard curve for magnolol was linear (r > 0.999) over the concentration range of 2-1 000 ng/mL, with a lower limit of quantification of 2 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 12% and the accuracy (relative error) was <5% at three quality control levels. This simple, fast and highly sensitive method was fully validated and successfully applied to a clinical pharmacokinetic study of magnolol in rats after oral administration.

In vitro and in vivo evaluation of Triptolide-loaded pluronic P105 polymeric micelles.

Thin film method was applied successfully to prepare Triptolide (TP)-loaded micelles system. With a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the TP-loaded micelles had a mean size of 84.3±6.4 nm with a spherical shape. The in vitro release profiles indicated that the release of TP from the micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic study in rats, in which AUC of the micelles formulation were 4.7-fold higher than that of TP injection. The biodistribution study in rats showed that the TP-loaded micelles not only decreased drug uptake by liver, but also increased distribution of drug in ovary. The present work demonstrated the feasibility of controlled delivery of TP utilizing micelles system.

Synthesis of solasodine glycoside derivatives and evaluation of their cytotoxic effects on human cancer cells.

Solasodine glycosides, such as solamargine, have been proved to be very important anti-cancer agents. In order to discover more potent cytotoxic agents and explore the preliminary structure activity relationship, a new series of solasodine glycosides 2-9 were synthesized via a transglycosylation strategy, and their cytotoxic activity against a panel of human cancer cell lines (MCF-7, KB, K562, and PC3 cells) were evaluated by MTT assays. The results indicated that compounds 2, 8, and 9 with the substitute moiety of rhamnose, 2-hydroxyethoxymethyl, and 1,3-dihydroxypropan-2-yloxy-methyl, respectively, exhibited quite strong anticancer activity. The underlying mechanism tests demonstrated that these compounds could induce apoptosis detected by DAPI staining, and Annexin V and propidium iodide binding. Cell cycle analysis indicated that the cancer cells were predominantly arrested at the G2/M phase when exposure to these compounds was examined by flow cytometry. These compounds may serve as lead candidates in the development of novel chemotherapeutics for cancer treatment.