Dual CD system-modified MEEKC method for the determination of clemastine and its impurities

A dual system of CDs was used for the first time in MEEKC with the aim of determining clemastine and its three main related impurities in both drug substances and tablets. The addition of methyl-β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin to the microemulsion pseudo-stationary phase was essential to increase the resolving power of the system to obtain a baseline separation among the compounds. The best microemulsion composition was identified by mixture design and the effects of the factors concentrations of CDs and voltage were investigated by a response surface study applying a Central Composite Design. In both cases, Derringer's desirability function made it possible to find the global optimum, which corresponded to the following combination: microemulsion, 89.8% 10 mM borate buffer pH 9.2, 1.5% n-heptane and 8.7% of SDS/n-butanol in 1:2 ratio; 18 mM methyl-β-cyclodextrin, 38 mM heptakis(2,6-di-O-methyl)-β-cyclodextrin, 17 kV. By applying these conditions, the separation was completed in about 5.5 min. The method was validated following International Conference on Harmonisation guidelines and was applied to a real sample of clemastine tablets.     

Elektroinitiierte kationische Polymerisation von Propylensulfid

Ohne Zusammenfassung     

Multivariate optimisation and validation of a capillary electrophoresis method for the analysis of resveratrol in a nutraceutical

A rapid and simple method based on capillary electrophoresis was developed for the quality control of nutraceuticals containing resveratrol. Setting the UV detector at 280nm, the optimisation involved the separation of 11 effervescent tablet components, including the active compounds vitamin C, vitamin B(2), flavanones and hydroxycinnamic acids. Flufenamic acid was employed as internal standard. The effects of background electrolyte concentration, acetonitrile percentage and voltage were investigated by means of response surface methodology, considering as responses the critical resolution values and analysis time. The optimum conditions were found by Derringer desirability function. The background electrolyte consisted of 23mM borate buffer, adjusted to pH 10.0 with 1M sodium hydroxide, containing 7% (v/v) acetonitrile. Temperature and voltage were set at 25 degrees C and 26kV, respectively. Applying these conditions, the analysis time was below 7min. The performances of the method were tested in terms of selectivity, robustness, linearity and range, accuracy and precision and system suitability, following ICH guidelines.     

Identification and determination of mainstream and sidestream smoke components in different brands and types of cigarettes by means of solid-phase microextraction-gas chromatography-mass spectrometry

The qualitative and quantitative determination of components of mainstream and sidestream smoke has been performed by solid-phase microextraction-gas chromatography-mass spectrometry. Several brands and types of cigarettes sold in Italy were considered: normal, mild, light, extra light, some with filter and some without. Extraction of the analytes was performed by means of solid-phase microextraction (SPME) and the optimisation of the extraction procedure was performed by experimental design, taking into consideration type of fiber polymer, exposure temperature and time. Sixty-seven components of mainstream and sidestream smoke were identified. The quantified compounds (by means of deuterium-labelled isotopologues) were benzene, toluene, p-xylene, m-xylene, pyridine, o-xylene, limonene, naphthalene, phenol and nicotine. Finally, a comparison between the chemical profile of smoke from the different cigarettes was made.     

Self-chemical ionization of diethylzinc

The self-chemical ionization of diethylzinc is examined by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry and semiempirical molecular orbital calculations. Electron impact of diethylzinc neutral produces the radical cation, C(4)H(15)Zn(+) (m/z x 122), which reacts further with the neutral (C(2)H(5))(2)Zn to give the following product ions: Zn(+) (m/z x 64), C(2)H(5)Zn(+) (m/z x 93), C(4)H(9)Zn(+) (m/z x 121), C(4)H(11)Zn(2)(+) (m/z x 187), and C(6)H(15)Zn(2)(+) (m/z x 215). To determine the structure and pathways for production of these ions, monoisotopic (12)C(4)H(15)(64)Zn(+), (64)Zn(+) and (12)C(2)H(5)(64)Zn(+) were individually isolated and reacted with the neutral background. We also performed semiempirical molecular orbital calculations (ZINDO/1). The molecular orbital calculations and experimental data are consistent in predicting that the ethyl group on the diethylzinc cation carries the positive charge. Copyright 1999 John Wiley & Sons, Ltd.     

High-performance liquid chromatographic assay of erythromycin from biological matrix using electrochemical or ultraviolet detection

Two chromatographic methods were developed for the determination of erythromycin A (EA) residues in animal tissues (muscle, liver, kidney and fat of cattle, pigs and poultry) and cow's milk. In addition to a more traditional method using electrochemical detection, we developed an original alternative method based on UV detection at 236 nm, by pretreating to create a chromophore in the molecule. An internal standard was used with both methods to check the variability of the analytical system. Analysis times and performance were compared. The recovery of EA from various matrices was greater than 95%. For both methods the quantification limit for EA was 0.25 microgram ml-1 for plasma, 0.025 microgram g-1 for milk and 0.125 microgram g-1 for the other biological matrices. The methods can be used to check for EA residues in these matrices; in fact, the statutory maximum residue limits (MRLs) of EA are 0.4 microgram g-1 in muscle, kidney, liver and fat of beef cattle, sheep, pigs and poultry, and 0.04 microgram g-1 in cow's and sheep's milk.     

Application of Experimental Design Methodologies in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: A Review

Chirality is one of the major issues in pharmaceutical research and industry. Capillary electrophoresis (CE) is an interesting alternative to the more frequently used chromatographic techniques in the enantioseparation of pharmaceuticals, and is used for the determination of enantiomeric ratio, enantiomeric purity, and in pharmacokinetic studies. Traditionally, optimization of CE methods is performed using a univariate one factor at a time (OFAT) approach; however, this strategy does not allow for the evaluation of interactions between experimental factors, which may result in ineffective method development and optimization. In the last two decades, Design of Experiments (DoE) has been frequently employed to better understand the multidimensional effects and interactions of the input factors on the output responses of analytical CE methods. DoE can be divided into two types: screening and optimization designs. Furthermore, using Quality by Design (QbD) methodology to develop CE-based enantioselective techniques is becoming increasingly popular. The review presents the current use of DoE methodologies in CE-based enantioresolution method development and provides an overview of DoE applications in the optimization and validation of CE enantioselective procedures in the last 25 years. Moreover, a critical perspective on how different DoE strategies can aid in the optimization of enantioseparation procedures is presented.     

怀孕期头发中一些元素含量的变化趋势

用同步辐射激发X射线荧光分析,对11个产妇怀孕期间头发内一些元素含量的变化趋势进行了测量,在各自对比的基础上,得到了一些结果。     

Development of a capillary electrophoresis method for the assay of ramipril and its impurities: an issue of cis-trans isomerization

The development of a rapid and selective capillary electrophoresis method for the quantitation of ramipril and its eight main impurities in pharmaceutical dosage form is described. Ramipril and three of its impurities contain a proline-similar moiety which causes in solution the presence of interconverting cis-trans isomers with respect to the amide bond. The interplay between electrophoretic migration and isomerization may yield the presence of an undesired interconversion zone between the two isomer peaks in the electropherogram, depending on the experimental conditions. Different capillary electrophoresis operative modes and pseudostationary phases were evaluated, both in normal and reverse polarity, in order to find the essential analytical parameters which could make it possible to overcome this issue and thus accurately quantify the analytes. The best results were obtained by using microemulsion electrokinetic chromatography in reverse polarity, where all the compounds which undergo cis-trans interconversion migrate as a single narrow peak. Experimental design led to identification of the following optimised conditions: background electrolyte, microemulsion made by 88.95% of 90 mM phosphate pH 2.5, 1.05% of n-heptane and 10.00% of SDS/n-butanol in 1:2 ratio; voltage, -26 kV; temperature, 17°C. Applying these conditions, the baseline separation of the analytes was obtained in about 10 min. Validation of the method following ICH guidelines was carried out and the procedure was applied to a real sample of ramipril tablets.