Assay method validation of triamcinolone acetonide (TA) to support the investigation of TA-loaded nanoparticles

Theaim of this study was to develop the valid analytical method which used for the assay of triamcinolone acetonide (TA) in the investigation of TA loaded nanoparticle formulations. High Performance Liquid Chromatography(HPLC) method was applied in  his study by using an Econosil column,C1810 m, 250x 4.6mm (Alltech Associates Inc, PA,USA )as the stationary phase. Themobile phase consisted of a composition of acetonitrile (ACN) and 20mM phosphate buffer solution (pH 4.2) in the proportion of 50:50 v/v. The HPLCassay of TA was validated for selectivity, linearity, precision, ecovery (accuracy),sensitivity and stability of TA during the assay. Results showed that the concentration of TA in the sample scan be determined against the standard in the concentration range of calibration curve. The system precision and level of recovery were considered to be acceptable, and the method was selective and sensitive.Key words:triamcinoloneacetonide,assay,validatio

Role of intestinal P-glycoprotein in the plasma and fecal disposition of docetaxel in humans

Multidrug resistance (MDR)-1-P-glycoprotein (P-gp) is a drug-transporting protein that is abundantly present in biliary ductal cells and epithelial cells lining the gastrointestinal tract. Here, we have determined the role of P-gp in the metabolic disposition of the antineoplastic agent docetaxel (Taxotere) in humans. Pharmacokinetic profiles were evaluated in five cancer patients receiving treatment cycles with docetaxel alone (100 mg/m2 i.v. over a 1-h period) and in combination with a new potent inhibitor of P-gp activity, R101933 (200-300 mg b.i.d.). The terminal disposition half-life and total plasma clearance of docetaxel were not altered by treatment with oral R101933 (P > or = 0.27). The cumulative fecal excretion of docetaxel, however, was markedly reduced from 8.47 +/- 2.14% (mean +/- SD) of the dose with the single agent to less than 0.5% in the presence of R101933 (P = 0.0016). Levels of the major cytochrome P450 3A4-mediated metabolites of docetaxel in feces were significantly increased after combination treatment with R101933 (P = 0.010), indicating very prominent and efficient detoxification of reabsorbed docetaxel into hydroxylated compounds before reaching the systemic circulation. It is concluded that intestinal P-gp plays a principal role in the fecal elimination of docetaxel by modulating reabsorption of the drug after hepatobiliary secretion. In addition, the results indicate that inhibition of P-gp activity in normal tissues by effective modulators, and the physiological and pharmacological consequences of this treatment, cannot be predicted based on plasma drug monitoring alone