Simultaneous Determination of Choline Citrate and Acetylmethionine in Injectable Solutions by High Performance Liquid Chromatography

Choline citrate (CC) and acetylmethionine (AM) are lipotropic drugs used in several pharmaceutical formulations. The objective of this research was to develop and validate a high performance liquid chromatographic (HPLC) method for simultaneous determination of CC and AM in injectable solutions, aiming its application in routine analysis for quality control of these pharmaceutical formulations. The method was validated using a Shim-Pack (R) C18 (250 x 4.6 mm, 5 mu m) column. The mobile phase was constituted of 25 mM potassium phosphate buffer solution, pH 5.7, adjusted with 10 % orthophosphoric acid, acetonitrile and methanol (88:10:2, v/v/v). The flow rate was 1.1 mL.min(-1) and the UV detection was made at 210 nm. The analyses were made at room temperature (25 +/- 1 degrees C). The method is precise, selective, accurate and robust, and was successfully applied for simultaneous quantitative determination of CC and AM in injectables.

Influence of Urea, Isopropanol, and Propylene Glycol on Rutin In Vitro Release from Cosmetic Semisolid Systems Estimated by Factorial Design

Rutin, one of the major flavonoids found in an assortment of plants, was reported to act as a sun protection factor booster with high anti-UVA defense, antioxidant, antiaging, and anticellulite, by improvement of the cutaneous microcirculation. This research work aimed at evaluating the rutin in vitro release from semisolid systems, in vertical diffusion cells, containing urea, isopropanol and propylene glycol, associated or not, according to the factorial design with two levels with center point. Urea (alone and in association with isopropanol and propylene glycol) and isopropanol (alone and in association with propylene glycol) influenced significant and negatively rutin liberation in diverse parameters: flux (g/cm2.h); apparent permeability coefficient (cm/h); rutin amount released (g/cm2); and liberation enhancement factor. In accordance with the results, the presence of propylene glycol 5.0% (wt/wt) presented statistically favorable to promote rutin release from this semisolid system with flux = 105.12 8.59 g/cm2.h; apparent permeability coefficient = 7.01 0.572 cm/h; rutin amount released = 648.80 53.01 g/cm2; and liberation enhancement factor = 1.21 0.07.

Gastro-resistant Pellets of Didanosine obtained by Extrusion and Spheronization: Assessing the Production Process

The aim this work was develop gastro-resistant pellets of didanosine as well as study the impact on the pellets properties, regarding the way as the binder was added and drying process used. The pellets formation was accompanied by analysis of morphological parameters and didanosine dissolution. In the most cases, pellets showed diameter around 1.0 mm and shape parameters acceptable. The variations of the process did not interfere significantly in pellets size. In turn, drying in fluid bed favored the dissolution of didanosine, in contrast to binder addition on powder form that impaired. In another hand, this last resulted in the best aspect factor (about 1.1). Gastro-resistant pellets showed adequate dissolution, compatible with this type of dosage form. The variables of process studied enabled obtain pellets with characteristics of shape and dissolution just slightly different, indicating flexibility of the formulation for production of gastro-resistant pellets of didanosine.

Ultrasound-Assisted Synthesis of Symmetrical Biaryls by Palladium-Catalyzed Homocoupling of Aryl n-Butyl Tellurides

An ultrasound-assisted synthesis of symmetrical biaryls with electron-withdrawing or -donating substituents is described and illustrated by palladium-catalyzed homocoupling reaction of aryl tellurides. This procedure offers easy access to biaryls in short reaction time, and the products are achieved in good to excellent yields.

Simultaneous determination of econazole nitrate, main impurities and preservatives in cream formulation by high performance liquid chromatography

A reversed-phase high performance liquid chromatographic (RP-HPLC) method for determination of econazole nitrate, preservatives (methylparaben and propylparaben) and its main impurities (4-chlorobenzl alcohol and alpha-(2,4-dicholorophenyl)-1H-imidazole-1-ethanol) in cream formulations, has been developed and validated. Separation was achieved on a column Bondclone (R) C18 (300 mm x 3.9 mm i.d., 10 mu m) using a gradient method with mobile phase composed of methanol and water. The flow rate was 1.4 mL min(-1), temperature of the column was 25 C and the detection was made at 220 nm. Miconazole nitrate was used as an internal standard. The total run time was less than 15 min, The analytical curves presented coefficient of correlation upper to 0.99 and detection and quantitation limits were calculated for all molecules. Excellent accuracy and precision were obtained for econazole nitrate. Recoveries varied from 97.9 to 102.3% and intra- and inter-day precisions, calculated as relative standard deviation (R.S.D), were lower than 2.2%. Specificity, robustness and assay for econazole nitrate were also determined. The method allowed the quantitative determination of econazole nitrate, its impurities and preservatives and could be applied as a stability-indicating method for econazole nitrate in cream formulations. (C) 2008 Elsevier B.V. All rights reserved.

Nucleophilic Addition of Potassium Alkynyltrifluoroborates to D-Glucal Mediated by BF(3)center dot OEt(2): Highly Stereoselective Synthesis of alpha-C-glycosides

A convenient, mild and highly stereoselective method for C-glycosidation (alkynylation) of D-glucal with various potassium alkynyltrifluoroborates, mediated by BF(3)center dot OEt(2) and involving oxonium intermediates, preferentially provides the alpha-acetylene glycoside products with good yields.

Quantitative Determination of Dimethylaminoethanol in Cosmetic Formulations by Nuclear Magnetic Resonance Spectroscopy

A nuclear magnetic resonance (NMR) spectroscopic method was validated for the quantitative determination of dimethylaminoethanol (DMAE) in cosmetic formulations. The linearity in the range from 0.5000 to 1.5000 g (DMAE salt/mass maleic acid) presents a correlation coefficient > 0.99 for all DMAE salts. The repeatability (intraday), expressed as relative standard deviation, ranged from 1.08 to 1.44% for samples and 1.31 to 1.88% for raw materials. The detection limit and quantitation limit were 0.0017 and 0.0051 g for DMAE, 0.0018 and 0.0054 g for DMAE bitartrate, and 0.0023 and 0.0071 g for DMAE acetamidobenzoate, respectively. The proposed method is simple, precise, and accurate and can be used in the quality control of raw materials and cosmetic gels containing these compounds as active substances.

Organocatalytic asymmetric aldol reactions mediated by a cysteine-derived prolinamide

In this Letter, a cysteine-derived prolinamide is described to act as a robust and effective organocatalyst for enantioselective aldol reactions. (c) 2008 Elsevier Ltd. All rights reserved.

Micromethod for Quantification of Carbamazepine, Phenobartital and Phenytoin in Human Plasma by HPLC-UV Detection for Therapeutic Drug Monitoring Application

A simple, rapid, selective and sensitive analytical method by HPLC with UV detection was developed for the quantification of carbamazepine, phenobarbital and phenytoin in only 0.2 mL of plasma. A C18 column (150 x 3.9 mm, 4 micra) using a binary mobile phase consisting of water and acetonitrile (70:30, v/v) at a flow rate of 0.5 mL/min were proposed. Validation of the analytical method showed a good linearity (0.3 to 20.0 mg/L for CBZ, 0.9 to 60.0 mg/L for PB and 0.6 to 40.0 mg/L for PHT), high sensitivity (LOQ: 0.3, 0.9 and 0.6 mg/L respectively). The method was applied for drug monitoring of antiepileptic drugs (AED) in 27 patients with epilepsy under polytherapy.

Quantitative Determination of Gemifloxacin Mesylate in Tablets by Capillary Zone Electrophoresis and High Performance Liquid Chromatography

The aim of this study was to develop and validate selective and sensitive methods for quantitative determination of an antibacterial agent, gemifloxacin, in tablets by high performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE). The HPLC method was carried out on a LiChrospher (R) 100 RP-8e, 5 mu m (125 x 4 mm) column with a mobile phase composed of tetrahydrofuran-water (25:75, v/v) with 0.5 % of triethylamine and pH adjusted to 3.0 with orthophosphoric acid. The CZE method was performed using 50 mM sodium tetraborate buffer (pH 8.6). Samples were injected hydrodynamicaly (0.5 psi, 5 s) and the electrophoretic system was operated under normal polarity, at +20 kV and capillary temperature of 18 degrees C. A fused-silica capillary 40.2 cm (30 cm effective length) x 75 mu m i.d. was used. Both, HPLC and CZE could be interesting and efficient techniques to be applied for quality control in pharmaceutical industries.

Development and validation of a method for quantitative determination of econazole nitrate in cream formulation by capillary zone electrophoresis

A simple, fast, inexpensive and reliable capillary zone electrophoresis (CZE) method for the determination of econazole nitrate in cream formulations has been developed and validated. Optimum conditions comprised a pH 2.5 phosphate buffer at 20 mmol L(-1) concentration, +30 kV applied voltage in a 31.5 cm x 50 mu m I.D. capillary. Direct UV detection at 200 nm led to an adequate sensitivity without interference from sample excipients. A single extraction step of the cream sample in hydrochloric acid was performed prior to injection. Imidazole (100 mu g mL(-1)) was used as internal standard. Econazole nitrate migrates in approximately 1.2 min. The analytical curve presented a coefficient of correlation of 0.9995. Detection and quantitation limits were 1.85 and 5.62 mu g mL(-1), respectively. Excellent accuracy and precision were obtained. Recoveries varied from 98.1 to 102.5% and intra- and inter-day precisions, calculated as relative standard deviation (RSD), were better than 2.0%. The proposed CZE method presented advantageous performance characteristics and it can be considered suitable for the quality control of econazole nitrate cream formulations. (c) 2008 Elsevier B.V. All rights reserved.

Stereoselective synthesis of the dolastatin units by organotrifluoroborates additions to alpha-amino aldehydes

Dolastatin units were synthesized from the 1,2-addition reactions of potassium allyl or crotyltrifluoroborate salts to aldehyde derivatives from natural amino acids. The reactions were carried out in presence of a phase-transfer catalyst in a biphasic medium at room temperature and excellent yields (>89-93%) and stereoselective (>90:10 to 98:2) were obtained. The dolastatin units 8 and 14a-b were obtained after three steps in good overall yields (50-62%). (C) 2007 Elsevier Ltd. All rights reserved.

Rutin association with ethylhexyl methoxycinnamate and benzophenone-3: In vitro evaluation of the photoprotection effectiveness by reflectance spectrophotometry

There is a world tendency to the development of sunscreens possessing reduced concentration of UV filters and, yet, with high UVA-UVB protection. This research work proposes the development and in vitro efficacy evaluation of sunscreens containing rutin, an antioxidant flavonol, associated or not to UVA (benzophenone-3) and UVB (ethylhexyl methoxycinnamate) filters. Formulations were in vitro assayed by reflectance spectrophotometry with integrated sphere, regarding the following parameters: estimated sun protection factor (SPF), critical wavelength (nm) and UVA/UVB ratio. Rutin 0.1% w/w photoprotection efficacy presented dependent of the concentration and presence of the UVA and UVB filters, and it was verified synergism on the SPF elevation, from 7.34 +/- 0.24 to 9.97 +/- 0.18, when the flavonoid was associated with the filters in minimum concentrations. Isolated rutin exerted UVA protection superior to the formulation not added to UV filters and their associations.

Extractive Fermentation of Clavulanic Acid by Streptomyces DAUFPE 3060 Using Aqueous Two-Phase System

The influence of four variables, specifically PEG molar mass (400, 1,000, and 8,000 g/mol), concentrations of PEG and phosphate salts (15, 20, and 25% for both), and agitation intensity (110, 150, and 200 rpm), on clavulanic acid (CA) extraction by extractive fermentation with PEG/phosphate salts aqueous two-phase system was investigated in shaken flasks using a 2(4-1)-fractional factorial design. After selection of the two most significant variables (agitation intensity and PEG molar mass), an optimization study conducted according to a 2(2)-central composite design revealed that 25% PEG 8,000 g/mol and phosphate salts at 240 rpm (run 6) were the best conditions for the extractive fermentation, leading to the best results in terms of partition coefficient (k = 8.2), yield of CA in the PEG-rich phase (eta(T) = 93%) and productivity (P = 5.3 mg/Lh). As a first attempt to make a scale-up of these results, the effectiveness of the extractive fermentation was then checked in a bench-scale bioreactor under conditions as close as possible to the optimum ones determined in flasks. The highest CA concentration obtained in the PEG-rich phase (691 mg/L) was 30% higher than in flasks, thus demonstrating the potential of such a new process, integrating the production and extraction steps, as a promising, low-cost tool to obtain high yields of this and similar products. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 27: 95-103, 2011

Biochemical and biophysical characterization of lysozyme modified by PEGylation

PEGylation is a strategy that has been used to improve the biochemical properties of proteins and their physical and thermal stabilities. In this study, hen egg-white lysozyme (EC 3.2.1.17; LZ) was modified with methoxypolyethylene glycol-p-nitrophenyl carbonate (mPEG-pNP, MW 5000). This PEGylation of LZ produced conjugates that retained full enzyme activity with glycol chitosan, independent of degree of enzyme modification; its biological activity with the substrate Micrococcus lysodeikticus was altered according to its degree of modification. The conjugate obtained with a low degree of mPEG-pNP/NH(2) modification was studied by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), demonstrating a spectral peak at m/z 19,988 Da with 77% of its original enzymatic activity. Spectroscopic studies of Fourier transform infrared (FIR) and circular dichroism (CD) did not show any relevant differences in protein structure between the native and conjugate LZ. Studies of the effects of pH and temperature on PEGylated LZ indicated that the conjugate was active over a broad pH range, stable at 50 degrees C, and demonstrated resistance to proteolytic degradation. (C) 2010 Elsevier B.V. All rights reserved.