Determination of endothelin antagonist BMS182874 in plasma by high-performance liquid chromatography.

A simple and rapid high performance liquid chromatography (HPLC) method was developed for the determination of BMS182874 (BMS) in mouse plasma. The drug was extracted from plasma by a liquid-liquid extraction process. The method consists of reversed-phase chromatography using a Thermo Hypersil-Keystone RP-18 5 microm, 250 x 2.1 mm column and UV spectrophotometer detection at 255 nm. The mobile phase consists of 45% (v/v) acetonitrile: 55% (v/v) trifluoroacetic acid (0.015% v/v; pH 3.0) at a flow rate of 0.6 ml/min. Validity of the method was studied and the method was precise and accurate with a linearity range from 100 ng/ml to 1000 ng/ml. The extraction efficiency was found to be 81, 84 and 87% for 100, 500 and 1000 ng/ml, respectively for spiked drug in plasma. The limit of quantification and limit of detection were found to be 50 and 10 ng/ml, respectively in plasma. Within-day and between-day precision expressed by relative standard deviation was less than 4% and inaccuracy did not exceed 4%. The assay was also used to analyze samples collected during animal studies. The suitability and robustness of the method for in vivo samples were confirmed by analysis of BMS from mouse plasma and tissues dosed with BMS.

Nasal drug delivery of sumatriptan succinate.

The purpose of this work was to increase the nasal absorption of sumatriptan succinate by using bile salts. A rat in situ nasal perfusion technique was used to examine the rate and extent of absorption of sumatriptan succinate. In vitro enzymatic drug degradation studies were carried out with rat nasal washings. Various experimental conditions such as nasal perfusion rate, pH of the perfusion medium and concentrations of absorption enhancers such as sodium deoxycholate, sodium caprate, sodium tauroglycocholate and EDTA were optimized. In vivo studies were carried out for the optimized formulation in rabbits and the pharmacokinetics parameters of nasal solution were compared with marketed nasal solutions. Nasal absorption of sumatriptan succinate was pH dependent. It was found maximum at pH 5.5 and decreased at higher pH values. In in vitro enzymatic degradation studies, no measurable degradation was observed during the first week. The extent of drug absorption was increased by absorption enhancers. Sodium deoxycholate appeared to be more effective for enhancing the nasal absorption of sumatriptan succinate than the other absorption enhancers. The order of increasing absorption of sumatriptan succinate caused by theenhancers was sodium deoxycholate > sodium caprate > sodium tauroglycocholate > EDTA.