Biomedical subjects
Publications and source records attributed to G Szepesi.
As a rarity in professional literature, the authors raise the case of a 37-year-old female patient who developed gastric antrum intramural haematoma, producing the clinical symptoms of III. grade pyloric stenosis, as a complication of a peptic duodenal ulcer. The authors point out this complication as a rarity.
The following methods are described for the analytical investigation of pipecuronium bromide. 1. HPLC method. Of the several systems tried for the separation and quantification of impurities and degradation products the best results were obtained using silica as the stationary phase and 43:43:14 mixture of methanol, acetonitrile and concentrated aqueous ammonia containing 0.1 mole/l each of ammonium chloride and ammonium carbonate as the eluent. The validation of this method is presented. The above described aggressive eluent can be successfully replaced by an ion-pairing system using silica as the stationary phase and 96:4 mixture of acetonitrile and water containing 0.1 mole/l sodium perchlorate as the eluent. 2. Thin-layer chromatography. TLC systems are described for the separation and densitometric quantification of the impurities and degradation products of pipecuronium bromide. 3. Spectrophotometry. Two methods are described. The ester groups of the molecule can be determined by the iron(III)-hydroxamate method while for the ion-pair extraction of the quaternary ammonium steroid picric acid or bromthymol blue are used as the reagents. 4. Titrimetry. In addition to the titration with acetous perchloric acid for the assay of the bulk material a microtitration method is described for the determination of pipecuronium bromide in individual lyophylized ampoules (potentiometric titration with 0.1 M silver nitrate).
Ruggedness is a measure of the reproducibility of the individual test results when the procedure is used repeatedly to determine the same homogeneous sample in a variety of specified experimental conditions. Ruggedness testing can be divided into two major groups: Type-A, when the influence of the changed environmental conditions (different equipment, analysts, etc.) on the analytical performance parameters and results are tested, and Type-B, when the effect of variation in the experimental conditions are checked. In the latter case, Type-B group can be further classified into two major subgroups: ruggedness testing of sample preparation and chromatographic separation. Checking sample preparation for ruggedness testing includes the investigation of various sample preparation procedures, such as: liquid-liquid extraction, solid phase extraction, direct sample introduction and derivative formation. The investigation of column-to-column variability, changes in the instrumental and experimental conditions belongs to the ruggedness testing of chromatographic separation. In this paper the basic principles of selection for experimental variables for various ruggedness tests are discussed introducing a new possibility to design multivariable-multicriteria system, and the evaluation of a single-variable-single-criterion system, as well. In general, from the work introduced in this paper, it can be concluded that when new analytical methods are developed, it is quite important to be aware the sensitivity of the method to variations in the specified conditions. For adequate performance of ruggedness testing: a) the factors (variables) which have significant influence on the chromatographic results can be firstly selected, b) maximum acceptable deviations from the prespecified experimental conditions can be decided, and c) the acceptable deviations from the values of the prespecified analytical performance parameters can be defined.
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The most important steps in the validation of high-performance liquid chromatographic (HPLC) methods are discussed. The establishment of system suitability data and the assessment of peak purity are demonstrated on the example of bisquaternary amino steroids. For the recognition of incomplete resolution of adjacent peak pairs, the absorbance-ratio method in which the ratio of absorbances at two preselected wavelengths are plotted as a function of time in combination with the separation of sample components subjected to various chemical and physico-chemical treatments (stress conditions) is applied. The separation power and performance of the HPLC systems are characterized by the system resolution (SR) and system selectivity (SS). The special demands of stability-indicating methods are summarized.
Different analytical tasks in the pharmaceutical analysis can be classified according to the separation problems into three main groups: trace analysis, assay methods and separation of closely related compounds including isomers. The most important requirements of high-performance liquid chromatographic (HPLC) methods with respect of the separation problems are summarized. Considerations and recommendations for the selection of the most applicable HPLC system to solve particular analytical problems are discussed. HPLC methods can be compared on the basis of the system resolution (SR) and system selectivity (SS). Criteria developed for the characterization of HPLC methods considering the difficulties created by the different analytical problems are established. The principles of the selection of the most applicable separation systems are demonstrated through some practical examples in pharmaceutical analysis.
The application of solvent optimization to the development of isocratic reversed-phase liquid chromatography has been reported in several publications. Two different approaches to solvent optimization for controlling band spacing for the maximum resolution of samples are "solvent strength" and "solvent type" optimization. To improve the separation selectivity further the combination of these two approaches was examined, as a (global) optimum mobile phase composition requires the optimization of the solvent strength by varying the percentage of organic component and of the solvent selectivity of methanol, acetonitrile, tetrahydrofuran and water. It was found that the combination of "solvent strength" and "solvent type" optimization provides a markedly better separation than either procedure alone.
Optimization of selectivity in normal-phase chromatography was studied. Using the same optimization criteria (Rs,min, Dmin, Rsb and Rsa) as in Part I the possible combination of "solvent strength" optimization by variation of the percentage of polar modifier in the less polar mobile phase and "solvent type" optimization by measuring the solvent selectivity of chloroform, acetonitrile, tetrahydrofuran and dioxane was examined. From the results it can be concluded that by replacement of medium-polarity solvents (chloroform, acetonitrile, tetrahydrofuran and dioxane) in the mobile phase, the selectivity of the separation can be significantly improved as the elution order is a function of solvent type belonging to Class P. In the separation of a steroid mixture dioxane provides the best properties for improving band spacing.
The most important problems of enantiomeric separations using chiral eluents are discussed. The methods have been compared with respect to enantiomeric purity of reagents, reagent selection and separation variables. The most important considerations for methods based on inclusion-complexation with different CDs and on using chiral counter ions are summarised and compared. A new possibility for the separation of enantiomeric compounds with the aid of a combination of ion-pair and inclusion-complex formation has been introduced. As a consequence of this investigation, the selectivity of the separation can be significantly improved; those ionic isomers and enantiomers which cannot be separated or are unsatisfactorily separated by ion-pair chromatography or by inclusion-complex formation, can be separated by the combined technique. Comparison of methods applicable for enantiomeric separations is also given with respect to solving specific analytical tasks in the field of pharmaceutical analysis.
The effects of various inorganic cations and anions on the chromatographic behaviour of insulin and its derivatives have been investigated. It was shown that on an octadecylsilica column at a given eluent composition the retention of insulins depends primarily on the nature of the anions. The cations have a secondary effect, depending on their size and coordination ability. The mechanism of the effect of the ions is complex. It includes the formation of ion pairs, their influence on dissociation processes, a silanophilic effect, coordination processes and changes in the structures of the insulins.
A reversed-phase displacement chromatographic method has been developed for the purification of bovine and porcine insulin samples. Up to 500 mg of raw insulin could be purified on a Nucleosil C8 analytical column using a methanol-containing phosphate buffer carrier and a cetrimide-containing displacer. A proinsulin contamination level as low as 100 ppm in the collected fractions could be achieved.
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Quantitative thin-layer chromatography was used to study the hydroxo-, cyano- and dicyanocobalamin transformation equilibria. A new stereoisomer of cyanocobalamin was shown to be formed from dicyanocobalamin on the chromatographic plate. The formation, stability and UV spectrum of this compound (isocyanocobalamin) was studied.
A new quantitative TLC method was developed for the determination of ethinylestradiol in tablets. The possible adsorption of ethinylestradiol on the starch can be avoided by enzymatic degradation, which enabled the easy extraction of the active ingredients from the tablet powder. The quantitative evaluation of the separated compounds was performed by densitometry at a wavelength of 280 nm. The relative standard deviation of the method was found to be better than +/- 2.6% in every case except Ambosex tablet where this value was +/- 4.7%. On the basis of the results obtained the method can be proposed for the routine analysis of tablets containing small amount of ethinylestradiol.
Separation of eburnane alkaloids using reversed-phase high-performance liquid chromatography was investigated on muBondapak C18 in LiChrosorb RP-8 columns with acetonitrile-aqueous 0.01 M ammonium carbonate as eluent. The method can be successfully applied for the group separation of eburnane alkaloids as well as for the separation of stereoisomers and of ester homologues.
A new HPLC method was developed for the monitoring of the hydrolytic decomposition of 5-iodine-2'-desoxyuridine in aqueous solution and for the stability assay of this compound in formulation. The separation of 5-iodine-2'-desoxyuridine and its decomposition products (5-iodineuracil and uracil) was performed on a u Bondapack C18 column using a mixture of water and methanol as eluent. On the basis of the experimental data, the kinetic order and the rate-constants of both consecutive reactions were determined.
Urinary osmolarity was studied with the DDAVP test in 30 children in the late stage of glomerulonephritis or nephrosis syndrome, and in 12 control children. A restriction of the concentrating ability of the kidney was demonstrated in the cases accompanied by residual symptoms, in comparison to the healthy children and to the patients in lasting remission. In the cases examined histologically, tubular damage corresponding to the functional change could be demonstrated.