Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat.

The rapamycin analog, ridaforolimus, has demonstrated potent anti-proliferative effects in cancer treatment, and it currently is being evaluated in a range of clinical cancer studies. Ridaforolimus is an extremely lipophilic compound with limited aqueous solubility, which may benefit from formulation with polymeric micelles. Herein, we report the encapsulation of ridaforolimus in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE-PEG2000) via a solvent extraction technique. Micelle loading greatly improved the solubility of ridaforolimus by approximately 40 times from 200 µg/mL to 8.9 mg/mL. The diameters of the drug-loaded micelles were 33 ± 15 nm indicating they are of appropriate size to accumulate within the tumor site via the enhanced permeability and retention (EPR) effect. The DSPE-PEG2000 micelle formulation was dosed intravenously to rats at 10 mg/kg and compared to a control of ridaforolimus in ethanol/PEG 400. The micelle significantly increased the half-life of ridaforolimus by 170% and decreased the clearance by 58%, which is consistent with improved retention of the drug in the plasma by the micelle formulation.

High-performance liquid chromatography assay of gnetol in rat serum and application to pre-clinical pharmacokinetic studies.

A method of analysis of gnetol (2,3',5',6-tetrahydroxy-trans-stilbene) in biological fluids is necessary for the study of its kinetics and disposition in plants. A simple high-performance liquid chromatography (HPLC) method was developed for the determination of gnetol in rat serum using a reverse-phase, isocratic system. Separation was achieved using a Phenomenex® Luna C18(2) column with ultraviolet detection at 305 nm. The standard curves were linear ranging from 0.5 to 100 µg/ml. The mean extraction efficiency was >90.5%. Precision of the assay was <14% (R.S.D.), and was within 14% at the limit of quantitation (0.5 µg/ml). Bias of the assay was lower than 15%, and was within 15% at the limit of quantitation. The assay was applied successfully to the study of serum disposition of gnetol in rats.

High-performance liquid chromatographic analysis: applications to nutraceutical content and urinary disposition of oxyresveratrol in rats.

A high-performance liquid chromatographic (HPLC) method was developed for the analysis of the stilbene, oxyresveratrol. This method involves the use of a Luna C(18) column with ultraviolet detection at 320 nm. The mobile phase consisted of acetonitrile, water and formic acid (30 : 70 : 0.04 v/v) with a flow rate of 0.6 mL/min. The calibration curves were linear over the range of 0.5-100.0 microg/mL. The mean extraction efficiency was between 98.9 and 109%. The precision of the assay was 0.069-18.4% (RSD%), and within 20% at the limit of quantitation (0.5 microg/mL). The bias of the assay was <15% and within 15% at the limit of quantitation. This assay was successfully applied to pre-clinical pharmacokinetic samples from rat urine and to nutraceutical product analysis.