Simultaneous determination of sulfamethoxazole and trimethoprim in biological fluids for high-throughput analysis: comparison of HPLC with ultraviolet and tandem mass spectrometric detection.

The comparison of two methods based on online solid phase extraction-liquid chromatography with UV (SPE-LC-UV) or mass spectrometry detection (SPE-LC-MS/MS) for the simultaneous quantification of sulfamethoxazole (SMZ) and trimethoprim (TMP) is presented. The methods were validated and proved to be accurate. The analysis of standard samples for SMZ at concentrations of 0.5, 1.5, 25 and 50microg/mL demonstrated a relative standard deviation of less than 6% for both methods (n=18), while TMP samples at concentrations of 0.05, 0.15, 1.5 and 5.0microg/mL were analyzed with R.S.D. of less than 4% (n=18). The method with mass spectrometric detection was approximately six times more sensitive than the method with ultraviolet detection. The total run time for the SPE-LC-MS/MS was 2.5min per sample as opposed to 18.0min for the SPE-LC-UV method. The method with MS detection in comparison with UV detection proved to be more rugged and was successfully applied to pharmacokinetics studies.

In vitro dissolution test of tamoxifen citrate preparations.

The Tamoxifen Citrate is available in oral tablet and is highly used as an endocrines therapy for breast cancer. Products from assorted makers bioavailability problems has been associated to the incomplete dissolution of the tablets. We determined the dissolution in vitro of five pharmaceutical preparations of the Tamoxifen Citrate available in the Brazilian market, Novaldex, Tecnotax, Zita, Tamoxifen (TEVA) and Tamoxifeno (PHARMACIA) all containing 10 mg of active drug. The methodology was conducted according to the in vitro dissolution test from USP XXIII. Other test such as mass uniformity, content uniformity and hardness were accomplished seeking to relate physical characteristics with the in vitro dissolution of these preparations. All the formulations presented liberation more than 75% of the active drug in 30 minutes. Any relationship was not observed between the in vitro dissolution, the average weight, the mass uniformity and the hardness of the tablets whereas the liberation was proportional to the tamoxifen citrate content. Although one of the tested products did present a higher dissolution profiles in comparison to the other tested preparation.

Synthesis of some 4-oxo-delta 2-thiazolin-2-ylhydrazones as potential antiprotozoal agents.

Several 4-oxo-delta 2-thiazolin-2-ylhydrazone derivatives 6 (6-1 - 6-19) derived from the cyclization reaction between the thiosemicarbazones 5 and homologous alpha-chloroacids were prepared. Only compound 6-2 was found to be active against Entamoeba histolytica and Trichomonas vaginalis.