Gy. Szász

Relationships between molecular connectivity indices, partition coefficients and chromatographic parameters

Etude faite sur une serie de derives de pyrido [2,1-a] pyrimidine et de pyrido [2,1-b] quinazoline

Determination of partition coefficients of pyrido[1,2-a]pyrimidin-4-one derivatives by traditional shake, thin-layer chromatographic and gas—liquid chromatographic methods

Abstract In the investigation of quantitative structure—activity relationships, one of the most important linear free-energy related parameters is the logarithmic value of water—1-octanol partition coefficients (log P ) and π values derived from that. Partition coefficients of eighteen pyrido[1,2- a ]pyrimidin-4-one compounds were measured for the water—1-octanol solvent system by spectrophotometric methods. R M values and corrected Δ I values of the compounds were also determined by thin-layer chromatographic and gas—liquid chromatographic methods, respectively. The excellent correlations found between these log P, R M and corrected Δ I values prove that liquid—liquid partition data can be obtained not only by thin-layer chromatography or high-performance liquid chromatography but also by gas—liquid chromatography.

HPLC Retention Index Scale for Nitrogen-Bridged Compounds

Abstract Retention indices of some nitrogen-bridged compounds having pharmacological activity have been determined. A retention index scale based on the relative retention of a homologous series of C3-C23 2-keto alkanes has been worked out. Linear relationships were found between RI and logP, allowing a prediction of retention indices. The relationships between the structures and the retention indices of these compounds have been interpreted.

SEPARATION AND IDENTIFICATION OF TOFISOPAM STEREOISOMERS BY HYPHENATED HPLC-CD TECHNIQUE

The published method allows the separation of the four isomers of the anxiolytic 2,3-diazepine derivative, tofisopam. Assignment for the peaks of the two central and two helical isomers is performed by using the chromatogram of the pure tofisopam enantiomers and also considering the conformer-equilibrium was suggested by previous authors. The detection has been made by CD. The in situ CD spectra of the peaks, obtained by stop-flow method, definitely show different chiral character.

Optimized and validated HPLC methods for compendial quality assessment. III. Testing of optical purity applying α1-acid-glycoprotein stationary phase

Abstract Since distomer impurity in the compendia enantiomer may indicate the lack of careful purification or an ability of racemization, the control of enantiomeric purity has growing significance. Although α1 - acid - glycoprotein (AGP) stationary phase was applied for the separation of a number of drug enantiomers, it was hardly used for testing of enantiomer purity. In this work the suitability of AGP column for compendial control of enantiomeric purity is illustrated by methods optimized through the selection of optimal quality (phosphate, acetate), pH (4.0; 5.5; 6.0; 7.0) and concentration (0.01, 0.03, 0.06 M) of the buffer-eluent and the best organic modifier (isopropanol, acetonitrile, dioxane). The chromatographic behavior of four basic, three acidic, and one neutral compound is interpreted. In the case of propranolol and ibuprofen, 5% impurity may be detected while, in the case of norgestrel, 2.5% of the impurity may be detected. Recommendations for compendial testing are presented.

Determination of Circular Dichroism and Ultraviolet Spectral Parameters of Norgestimate- and Other Delta4-3-Ketosteroid Oxime Isomers Via Normal Phase HPLC Method

The oxime formation reaction of therapeutical progestogen (levonorgestrel, levonorgestrel acetate, norethisterone), androgen (methyltestosterone, testosterone phenylpropionate) and anabolic (nortestosterone phenylpropionate) Delta(4)-3-ketosteroids has been investigated. The ketosteroid-hydroxylamine reaction was monitored by reversed phase HPLC system. It was established, that under the experimental conditions applied the oxime formation was complete within 2 h. The reaction leads to the formation of Z and E oxime isomers. The isomers of norgestimate (levonorgestrel 17-acetate oxime) and other Delta(4)-3-ketosteroid oximes have been separated by a new normal phase HPLC method. The identification (elution order assignation) and determination of the formation ratio of the isomers have been performed by 1H NMR spectroscopy on the basis of the chemical shift differences of 4-H signals. The on-line CD and UV spectra of the pure oxime isomers were recorded and then molar ellipticities and absorbances of the isomers were calculated in the wavelength range of 200-300 nm via parameter estimation method.

Some problems in the correlation of molecular parameters and the connectivity index

Abstract A study was made of 28 heterocyclic nitrogen-containing compounds and 68 of their alkyl derivatives. Their retention indices were determined on the stationary phases OV-1, OV-25, OV-225 and Carbowax 20M, and their molecular connectivity indices were obtained by the method of Kier. It was found that the four groups of compounds distinguished by cluster analysis corresponded to certain molecular properties, even without a regression correlation. A tree-graph produced from the data revealed those pairs of compounds and those structural differences which are not (or only slightly) differentiated by the connectivity index. The effect of the mean polarity of the stationary phase was used to evaluate the fit of the regression. By comparison of the statistical parameters of the various regression equations, a study was made of the roles played by the simple, valence, path and path-cluster indices in the value of the dependent variable.

Ion-Pair Chromatography of Nitrogen-Bridged Compounds on Silica Gel

Abstract New adsorption operations of high-performance ionpair chromatography have been investigated, using certain types of pharmacologically active nitrogen-bridged compounds. Various chromatographic data are reported. The effect of the counter ion concentration has been studied. Numerous examples of separations are presented.

Thin-layer chromatography of homopyrimidazole derivatives

The chromatographic behaviour of 14 homopyrimidazole derivatives has been studied on thin layers of silica gel, aluminium oxide and ammonia-saturated silica gel. The relationships between structure and chromatographic behaviour, as well as the most suitable systems for separating the individual derivatives, are discussed on the basis of RF values. The delta RMg values, showing the effect on the polarity, are given for certain functional groups.

6-Oxo-Morphinane Oximes: Pharmacology, Chemistry and Analytical Application

The permanent therapeutic importance of morphine derivatives in pain treatment has inspired continual synthetic efforts to modify the rigid pentacyclic systems in search for new selective analgesic agents. As a result, several morphinane oximes have been synthesized recently, which have the additional advantage of possessing an oxime group that can provide a method for selective determination of opiate alkaloids in biological matrices. The oximes of hydrocodone and oxycodone have stronger analgesic effect than the parent ketones and they also proved to be effective in preventing the respiratory depressant and hypotensive actions of fentanyl. In this work a review is given on the present status of oxime pharmacology, chemistry and analysis and also the oxime and O-methyl oxime formation of 6-oxo-morphinanes with therapeutic interest (codeinone, oxycodone, hydrocodone and 14-OH-codeinone). The oxime formation was monitored by reversed-phase HPLC and the chromatographic properties of oxime isomers have been characterized. The assignation of the individual isomers isolated by preparative HPLC was performed by (1)H NMR spectroscopy based on the chemical shift differences of the 5-H signals. In this way the isomeric ratio in the oxime products could also be determined. It was found that in the case of Delta(7)-6-oxo-morphinanes, depending on the substituents, the formation of the Z-isomer highly dominates (73-96%) over that of the E-isomer. However, for the saturated 7,8-(dihydro) derivatives the E-isomer is definitely preferred (>98%). In conclusion of a survey on the theoretical background of oxime isomerism, the conformational differences between the saturated and unsaturated morphinane systems were found responsible for the different E/Z ratios. On the basis of the isomeric ratio and the on-line CD and UV spectra of the pure isomers, the molar ellipticities and absorbancies of the isomers were calculated by a parameter estimation method.