ABSTRACT Carbamazepine (CBZ) is a drug used as anticonvulsant, especially in the treatment of epilepsy. For adequate control disease, treatment must achieve adequate blood concentrations, therefore, it is very important to control the levels of anticonvulsant drugs in biological matrices with suitable analytical methods. A simple and fast liquid chromatographic method with UV detection was developed and validated for the determination of CBZ in saliva. Chromatographic separation was achieved with a RP-18 column, using acetonitrile and water with triethylamine at pH 7,3 as mobile phase in isocratic elution mode, at a flow rate of 1 mL/min. The detection was done at 230 nm. and bromazepam at 1,5 μg/mL was used as IS. The run time was 5 min. The described method was linear over a range of 0,5 - 5,5 μg/mL. The intraassay and interassay precision, expressed as the RSD, were in the range of 0,67 - 2,93 % and 0,17 - 9,33 %, respectively, the extraction recoveries were between 100,67 – 100,69 %, the accuracy values ranged from −3,33 to 0,69 % and - 2,67 to 0,72 in intraday and interday analysis, respectively, and the assay demonstrated adequate selectivity and specificity. The LLOQ is below the therapeutic level, demonstrating an adequate sensitivity of the method. The results showed that the proposed method was found to be suitable for quantitative determination of CBZ in saliva.

ABSTRACT Risperidone, an antipsychotic drug, was determined in human serum, using an optimized liquid-liquid extraction for isolation from biological fluid, with ethyl acetate as extraction solvent. This sample extraction method was chosen to increase extraction efficiency and reduce matrix interferences. Quantitation was achieved by LC/DAD at 294 nm over the concentration range of 1 ng/mL to 60 ng/mL (r=0.999). Desipramine was used as internal standard (tR for Risperidone: 4.23; tR Desipramine: 7.31). Mobile phase was water: acetonitrile: triethilamine: glacial acetic acid (70:29.16:0.52: 0.33 v/v), using a Purosphere STAR RP-18e 250 × 4.5 mm (5µ) column. RSD, for the intra-assay study, was between 0.52 % – 2.09 % (n=3), and between 0.79 % −3.25 % (n=9) for the inter-assay. LOD was 0.40 ng/mL and LOQ was 0.87 ng/mL. Recovery percentage for the accuracy study was between 90.82% and 98.56% ((RSD ≤ 3.93). The method is simple, fast, precise, accurate, sensible and selective. This method was successfully applied to quantify risperidone in patient serum samples. In conclusion, the method is useful for quantitative determination of risperidone in human serum.

ABSTRACT A stability-indicating LC method was developed and validated for the determination of risperidone in tablets. Quantitation was achieved by LC/DAD at 294 nm over the concentration range of 25.00 μg/mL to 250.00 μg/mL. Mobile phase was a mixture of water: glacial acetic acid 0.50 %: triethylamine 0.80 %: acetonitrile (65.00: 0.32: 0.52: 34.16, v/v), using a Purosphere STAR RP-18e 250 × 4.5 mm (5μ) column, and paroxetine as internal standard. The method exhibited an adequate linearity (r = 0.999), selectivity, precision (RSD ≤ 0.847 %) and accuracy (recoveries from 99.55 % to 101.35 %). Risperidone was subjected to the stress conditions of oxidative, acid, base, thermal and photolytic degradation. Risperidone was found no degrade in basic or acid stress conditions, neither in thermal stress exposition (50, 70 and 100 °C) no at visible or UV stress conditions, during the time of the study. Only two degradation products were observed with peroxide oxidation, well resolved from analyte peak, proving the stability-indicating power of the method. The proposed method was found to be suitable for quantitative determination and the stability studies of risperidone in tablets.

Type 2 diabetes and obesity are possible risk factors for Alzheimer’s disease and these can be modified by physical activity and changes in dietary patterns, such as switching to a Mediterranean diet. This diet includes fruits, vegetables, olive oil, fish and moderate wine intake. These foods provide vitamins, polyphenols and unsaturated fatty acids. This diet should be able to reduce oxidative stress. The inflammatory response is also reduced by unsaturated fatty acids, resulting in a lower expression and a lower production of pro-inflammatory cytokines. The Cardiovascular protection is related to the actions of polyphenols and unsaturated fatty acids on the vascular endothelium. The Mediterranean diet also can improve cardiovascular risk factors such as dyslipidemia, hypertension and metabolic syndrome. These beneficial effects of the Mediterranean diet should have a role in Alzheimer’s disease prevention.

Introduction: Pediculosis capitis is a public health problem with a high prevalence. The emergence of parasite resistance to conventional pediculicide is of great concern worldwide. Objective: To develop alternatives pediculicide, effective and safe, based on the essential oil of Eucaliptus globulus. Method: Through bioassays active concentrations ranges of the essential oil were established, and proceeded to develop a standardized, stable, pharmaceutical form, evaluating its effects on our population. Results: The results showed 100% effectiveness; short time of death, ovicidal action, activity on the adhesion of the egg, and low toxicity. Discussion: In addition to great effect, the inability of the parasite to become resistant to the chemical composition of the essential oil makes this formulation an alternative to the problem of head lice solution.

Introducción: La pediculosis capitis es un problema de salud pública con una alta prevalencia. La aparición de resistencia del parásito a los pediculicidas convencionales es de gran preocupación a nivel mundial. Objetivo: Desarrollar alternativas pediculicidas, efectivas y seguras, en base al aceite esencial de Eucaliptus globulus. Método: A través de bioensayos se establecieron rangos de concentraciones activas del aceite esencial, y se procedió al desarrollo de una forma farmacéutica, estandarizada, estable, evaluando sus efectos en nuestra población. Resultados: Los resultados mostraron 100% de efectividad; corto tiempo de muerte, acción ovicida, actividad sobre la adherencia del huevo, y baja toxicidad. Discusión: Además de la gran efectividad, la imposibilidad del parásito de adquirir resistencia a la composición química del aceite esencial hace de esta formulación una solución alternativa al problema de la pediculosis.

A high performance thin-layer chromatographic (HPTLC) method for quantitative analysis of trazodone in human serum has been developed and validated. Trazodone was extracted with n-hexane: isoamyl alcohol (99:1). Chromatographic separation was performed on silica gel 60 F 254 HPTLC plates, with toluene: acetone: ethanol: ammonium (9:7:2:0.5, v/v/v/v) as mobile phase. Densitometric evaluation was carried out at 290 nm. There was no chromatographic interference between trazodone and its major metabolite, m-chlorophenilpiperazine (Rf 0.82 and 0.39, respectively). Regression analysis of the calibration plot revealed good linearity (r=0.999) over the range of 20.00 and 200.00 ng/band, corresponding to 0.20 and 2.00 ng/µL of trazodone in human serum after extraction process and applying 10 µL to the chromatographic plates. The % RSD of intra-assay and inter-assay precision, were in the range of 0.98% to 2.97% (n=3) and 1.06% to 3.54% (n=9), respectively. LOD and LOQ were found to be 0.016ng/µL, and 0.048ng/µL, and the recovery values, of trazodone from serum, were between 92.52 % and 96.73 %. This method was successfully applied to quantify trazodone in patient serum samples. In conclusion, the developed method might be useful for the quantitative determination of trazodone in human serum, as a tool to evaluate patient adherence to their pharmacotherapy with this drug.

A stability- indicating high performance thin layer chromatographic (HPTLC) method was developed and validated for the determination of enalapril maleate in tablets. Chromatographic separation was achieved on precoated silica gel F 254 HPTLC plates using a mixture of 1-buthanol, glacial acetic acid and water (12:3:5, v/v) as a mobile phase. Quantitative analysis was carried out at a wavelength of 207 nm. The method exhibitied an adequate linearity (r =0.998), selectivity, precision and accuracy. Enalapril was subjected to oxidative, hydrolytic, thermal and photolytic stress conditions, and was found degradation significantly in basic stress condition only, during the time of the study. The degradation products were well resolved from main peak, proving the stability-indicating power of the method. This method was successfully applied for quantitative analysis of enalapril maleate in tablets. Therefore, the method is suitable for quantitative determination and the stability studies of enalapril maleate in tablets.

A method using HPTLC for quantitation of nifedipine in serum was developed and validated. It includes a liquid-liquid extraction, and carbamazepine as internal standard. Chloroform: ethyl acetate: cyclohexane (19:2:2, v/v/v) was the mobile phase. The method showed good relationship (r = 0.996) (2.00 to 25.00 ng/band, corresponding to 0.02 and 0.25 ng/µL in serum). The % RSD of intra-assay and inter-assay, were between 0.57 and 3.56 and 1.16 to 3.60, respectively. LOD and LOQ were 0.72 and 0.86 ng/band, respectively. The recovery values were between 93 and 102%. Rf for nifedipine and carbamazepine were 0.31 and 0.10, respectively.

The chemical stability of enalapril drug substance and tablets was studied by a stability-indicating liquid chromatographic method. Stress testing was performed on drug substance under various conditions. Accelerated stability testing was carried out for different formulations of enalapril tablets. Chromatographic separation was achieved on a RP-18 column, using a mobile phase of methanol phosphate buffer at 1.0 mL min"1 and UV detection. Degradation of the drug substance was greater under hydrolytic conditions. After 180 days of accelerated stability testing most enalapril tablets showed more than 10% of degradation. Enalapril drug substance and tablets showed instability under stress and accelerated testing respectively, with possible implications on the therapeutic activity.

Verapamil is one of the frequently prescribed calcium channel blockers used in the treatment of hypertension and angina pectoris. Results of evaluations of the therapy have led to reports of toxic effects. This study presents several evidences that verapamil affects human cells. Scanning electrón microscopy observations of intact human erythrocytes indicated that they underwent morphological alterations as increasing verapamil concentrations starting from 5 µM changed their discoid normal shape, and finally to hemolysis. Fluorescence spectroscopy on isolated unsealed human erythrocyte membranes confirmed these outcomes. In fact, the assays showed that verapamil induced a significant increase of the anisotropy parameters and a modérate one of the generalized polarization, indicative of enhanced order at the acyl chain and polar head regions of the erythrocyte membrane lipid bilayer. X-ray diffraction experiments on dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine bilayers, classes of the major phospholipids present in both outer and inner sides of the erythrocyte membrane, respectively showed that verapamil perturbed the polar head and acyl chain regions of both lipid bilayers. These interactions were found to be stronger with DMPC bilayers. On the other hand, human SH-SY5Y neuroblastoma cells incubated with verapamil suffered a sharp decrease of cell viability.

An instrumental planar chromatography method for quantitative analysis of carbamazepine in saliva was developed. The linearity, precision, detection and quantification limits, accuracy and selectivity of the method were validated. The method was linear between 0.50 and 15.00 ng/spot, with a regression coefficient of 0.999. The intra-assay variation (repeatability) was between 5.1% and 7.4%, and the inter-assay (reproducibility) was between 5.6% and 7.4%. The detection limit was 0.18 ng, and the quantification limit was 0.54 ng. The method proved accurate, with a recovery percentage of 109.8%, and it was selective for the active principle tested. In conclusion, is a good method for the quantitative determination of carbamazepine in saliva