Fotouh R. Mansour

Solidification of floating organic droplet in dispersive liquid-liquid microextraction as a green analytical tool

Dispersive liquid-liquid microextraction (DLLME) is a special type of microextraction in which a mixture of two solvents (an extracting solvent and a disperser) is injected into the sample. The extraction solvent is then dispersed as fine droplets in the cloudy sample through manual or mechanical agitation. Hence, the sample is centrifuged to break the formed emulsion and the extracting solvent is manually separated. The organic solvents commonly used in DLLME are halogenated hydrocarbons that are highly toxic. These solvents are heavier than water, so they sink to the bottom of the centrifugation tube which makes the separation step difficult. By using solvents of low density, the organic extractant floats on the sample surface. If the selected solvent such as undecanol has a freezing point in the range 10-25°C, the floating droplet can be solidified using a simple ice-bath, and then transferred out of the sample matrix; this step is known as solidification of floating organic droplet (SFOD). Coupling DLLME to SFOD combines the advantages of both approaches together. The DLLME-SFOD process is controlled by the same variables of conventional liquid-liquid extraction. The organic solvents used as extractants in DLLME-SFOD must be immiscible with water, of lower density, low volatility, high partition coefficient and low melting and freezing points. The extraction efficiency of DLLME-SFOD is affected by types and volumes of organic extractant and disperser, salt addition, pH, temperature, stirring rate and extraction time. This review discusses the principle, optimization variables, advantages and disadvantages and some selected applications of DLLME-SFOD in water, food and biomedical analysis.

Ion Exclusion Chromatography of Aromatic Acids

The determination of aromatic acids by ion exclusion chromatography is challenging due to peak tailing and the long retention time of hydrophobic solutes. This review discusses the retention mechanisms and the factors affecting retention, eluents and detection methods used in ion exclusion chromatography of aromatic acids such as mono-, di-, tri- and tetra-carboxylic acids, amino acids, sulfonates and phenol. In addition, the different approaches used to improve the chromatographic separation of these compounds are also discussed. These approaches include introducing an internal gradient of the ionic strength, using vacancy ion exclusion chromatography, employing a hydrophilic cation exchange resin or adding a modifier such as heptanol to the dilute sulfuric acid mobile phase. The applications of these methods in the analysis of aromatic acids are provided with a table summarizing the stationary phases, the mobile phases and the detection methods.

Pharmaceutical and biomedical applications of dispersive liquid–liquid microextraction

Sample treatment is so crucial in pharmaceutical and biomedical analysis. Proper sample preparation protects the analytical instrument, increases the sensitivity, and enhances the selectivity by removing probable interfering substances. Dispersive liquid-liquid microextraction (DLLME) is one of the most important approaches in sample treatment. In normal DLLME, the organic droplet of the extractant is mixed with a dispersing solvent before being injected into the sample. After manual or mechanical shaking, the cloudy solution is centrifuged to break the formed emulsion. The organic phase is then separated and transferred to the analytical instrument. The dispersion process employed in DLLME dramatically increases the contact surface between the extractant and the sample, which enhances the extraction kinetics and efficiency. DLLME can be classified based on the dispersion technique or the density of the extractant. Accordingly, different modes of DLLME have evolved and been applied for drug analysis in biological fluids. This review discusses the principle of DLLME, the requirements of organic solvents used as extractants in each mode and the different factors affecting the extraction efficiency. Selected applications of the different DLLME modes in bio-pharmaceutical analysis have also been presented.

Separation methods for captopril in pharmaceuticals and biological fluids

Captopril (CAP) is an orally active angiotensin-converting enzyme (ACE) inhibitor and has been widely used for management of hypertension and congestive heart failure. CAP lacks an aromatic chromophore required for facile direct UV detection and also has two chiral centers. These factors can render the determination of CAP in complex matrices challenging. This review covers more than 20 years of analytical research on this drug, focusing mainly on pharmaceutical and biological applications. The primary separation techniques discussed are gas chromatography, liquid chromatography, and capillary electrophoresis. The structures of the CAP derivatizing agents as well as a table summarizing various HPLC methods are provided. A discussion of key recent chromatographic and electrophoretic methods for other ACE inhibitors is also present.

Development and Validation of Chemometric-Assisted Spectrophotometric Methods for Simultaneous Determination of Phenylephrine Hydrochloride and Ketorolac Tromethamine in Binary Combinations.

The present work describes new spectrophotometric methods for the simultaneous determination of phenylephrine hydrochloride and ketorolac tromethamine in their synthetic mixtures. The applied chemometric techniques are multivariate methods including classical least squares, principal component regression, and partial least squares. In these techniques, the concentration data matrix was prepared by using the synthetic mixtures containing these drugs dissolved in distilled water. The absorbance data matrix corresponding to the concentration data was obtained by measuring the absorbances at 16 wavelengths in the range 244-274 nm at 2 nm intervals in the zero-order spectra. The spectrophotometric procedures do not require any separation steps. The accuracy, precision, and linearity ranges of the methods have been determined, and analyzing synthetic mixtures containing the studied drugs has validated them. The developed methods were successfully applied to the synthetic mixtures and the results were compared to those obtained by a reported HPLC method.

Three Spectrophotometric Methods for Determination of Alogliptin Benzoate and Pioglitazone HCl in Combined Tablet Dosage Form

Abstract Three simple, accurate and precise spectrophotometric methods have been developed and validated for simultaneous determination of alogliptin benzoate and pioglitazone HCl in bulk and in tablet dosage form. Method I was area under curve method and it involved measurement of area at selected wavelength range; the selected wavelength range was 275-285 nm for ALG and 263-273 nm for PIO. Method II involved the use of first derivative of ratio spectra (1DD) using PIO (10 μg/mL) as a divisor for ALG determination, then peak amplitude at 300 nm was directly proportional to ALG concentration; and ALG 5 μg/mL as a divisor for PIO determination, then peak amplitude at 277 nm was directly proportional to PIO concentration. Method III was ratio difference method and it involved measurement of difference in amplitudes (ΔP) in the ratio spectra; ΔP292-238 was directly proportional to ALG concentration and ΔP260-239 was directly proportional to PIO concentration. The three proposed methods were linear over the range 5-30 μg/mL for ALG and 5-50 μg/mL for PIO. The methods were validated according to ICH guidelines. Statistical comparison of the proposed methods with the reported HPLC method using F and t tests showed no significant difference regarding both accuracy and precision.

Solvent-terminated dispersive liquid-liquid microextraction: a tutorial

Solvent-terminated dispersive liquid-liquid microextraction (ST-DLLME) is a special mode of DLLME in which a demulsifying solvent is injected into the cloudy mixture of sample/extractant to break the emulsion and induce phase separation. The demulsification process starts by flocculation of the dispersed microdroplets by Ostwald ripening or coalescence to form larger droplets. Then, the extractant either floats or sinks depending on its density as compared with that for the aqueous sample. The demulsifier should have high surface activity and low surface tension in order to be capable of inducing phase separation. The extraction efficiency in ST-DLLME is controlled by the same experimental variables of normal DLLME (n-DLLME) such as the type and volume of the extractant as well as the disperser. Other parameters such as pH and the temperature of the sample, the stirring rate, the time of extraction and the addition of salt are also important to consider. Along with these factors, the demulsifier type and volume and the demulsification time have to be optimized. By using solvents to terminate the dispersion step in DLLME, the centrifugation process is not necessary. This in turn improves precision, increases throughput, decreases the risk of contamination through human intervention and minimizes the overall analysis time. ST-DLLME has been successfully applied for determination of both inorganic and organic analytes including pesticides and pharmaceuticals in water and biological fluids. Demulsification via solvent injection rather than centrifugation saves energy and makes ST-DLLME easier to automate. These characteristics in addition to the low solvent consumption, the reduced organic waste and the possibility of using water in demulsification bestow green features on ST-DLLME. This tutorial discusses the principle, the practical aspects and the different applications of ST-DLLME.

A simple homemade spectrophotometer

A simple portable spectrophotometer was constructed and used to perform analytical experiments. The developed model uses available tools and materials such as light emitting diode lamps, compact discs, plastic and cardboard boxes and a cell phone camera to build a design that illustrates the major components of spectrophotometers. The spectra of serial concentrations of KMnO4 (50‒600 μM) were recorded and the values of absorbance were extracted at λmax to build the calibration curve. A linear relationship between the concentration and absorbance was obtained with the coefficient of determination 0.994. The model was also utilized to study the spectra of KMnO4, phenolphthalein and bromothymol blue in comparison with a Shimadzu UV-1800 spectrophotometer as a reference instrument. In spite of the differences in the observed spectra, the recorded λmax were almost identical to those measured by the developed model. The model was successfully used to determine the concentration of sodium alendronate through ligand-exchange complexation with ferric salicylate.

Development and Validation of Chemometric Spectrophotometric Methods for Simultaneous Determination of Simvastatin and Nicotinic Acid in Binary Combinations

BACKGROUND The development and introduction of combined therapy represent a challenge for analysis due to severe overlapping of their UV spectra in case of spectroscopy or the requirement of a long tedious and high cost separation technique in case of chromatography. Quality control laboratories have to develop and validate suitable analytical procedures in order to assay such multi component preparations. METHODS New spectrophotometric methods for the simultaneous determination of simvastatin (SIM) and nicotinic acid (NIA) in binary combinations were developed. These methods are based on chemometric treatment of data, the applied chemometric techniques are multivariate methods including classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS). In these techniques, the concentration data matrix were prepared by using the synthetic mixtures containing SIM and NIA dissolved in ethanol. The absorbance data matrix corresponding to the concentration data matrix was obtained by measuring the absorbance at 12 wavelengths in the range 216 - 240 nm at 2 nm intervals in the zero-order. The spectrophotometric procedures do not require any separation step. The accuracy, precision and the linearity ranges of the methods have been determined and validated by analyzing synthetic mixtures containing the studied drugs. CONCLUSION Chemometric spectrophotometric methods have been developed in the present study for the simultaneous determination of simvastatin and nicotinic acid in their synthetic binary mixtures and in their mixtures with possible excipients present in tablet dosage form. The validation was performed successfully. The developed methods have been shown to be accurate, linear, precise, and so simple. The developed methods can be used routinely for the determination dosage form.