HPLC and TLC enantioseparation of the nitro-positioned aryloxysubstituted aminopropanols.

An enantioseparation study of nitro-substituted aryloxyaminopropanols was performed using HPLC on a teicoplanin chiral stationary phase and TLC impregnated with L-aspartic and L-tartaric acid as chiral selectors. The type of substituent on the nitrogen in the hydrophilic part of molecule is essential for excellent separation by HPLC. L-aspartic acid seems to be a suitable chiral selector for enantioseparation by TLC.

HPLC separation of enantiomers of some potential beta-blockers of the aryloxyaminopropanol type using macrocyclic antibiotic chiral stationary phases. Studies of the mechanism of enantioseparation, Part XI.

The macrocyclic antibiotic type chiral stationary phases based on native vancomycin, teicoplanin and teicoplanin aglycone (Chirobiotic V, Chirobiotic T and Chirobiotic TAG) were used for the HPLC separation of enantiomers of potential beta-blockers of the aryloxyaminopropanol type with a morpholino moiety in the hydrophilic part of the molecule. The chromatographic results presented include: retention, separation and resolution factors along with the enantioselective free energy difference corresponding to the separation of the enantiomers. Comparison of the results obtained on the three macrocyclic chiral stationary phases showed that in most cases the teicoplanin aglycone is responsible for enantioseparation of morpholino derivatives. By application of these chiral stationary phase highest resolution factors were achieved with a polar organic mobile phase system.

HPLC enantioseparation of potential beta-blockers of the aryloxyaminopropanol type. Study of the mechanism of enantioseparation, Part VIII.

This paper presents the results of HPLC enantioseparation of derivatives of aryloxyaminopropanols obtained using six chiral stationary phases [macrocyclic antibiotic (vancomycin, teicoplanin, teicoplanin aglycone, and methylated teicoplanin aglycone) and cyclodextrin (beta and gamma)] and a mixture of methanol/acetonitrile/acetic acid/triethylamine (45/55/0.3/0.2) as the mobile phase. No significant difference was observed in the separation of the enantiomers on the vancomycin and teicoplanin chiral stationary phases. Comparing the separation of enantiomers on teicoplanin-based columns the retention factors were increased in the order: native teicoplanin < teicoplanin aglycone < methylated teicoplanin aglycone. The highest values of resolution were obtained on the column containing carbohydrate moieties. The presence of saccharide moieties in the chiral stationary phase plays an important role, together with charge interactions and steric interactions, in the separation of enantiomers of derivatives of aryloxyaminopropanol.

[HPLC determination of diperodon enantiomers in blood serum by using teicoplanin chiral stationary phase]. / HPLC stanovenie enantiomérov diperodonu v krvnom sére s pouzitím teikoplaninovej chiralnej stacionárnej fázy.

The chiral stationary phase on the base of teicoplanin and the polar-organic mobile phase methanol/acetonitrile/acetic acid/triethylamine 45/55/0.3/0.2 was used for the separation of diperodon enantiomers. The developed method was suitable to determine the enantiomers in blood serum up to 0.5 microg/ml. The degradation of diperodon enantiomers was studied in serum by an in vitro method and the experimental rate constants were determined.

[Separation of enantiomers of phenylcarbamic acid derivatives by HPLC method]. / Separácia enantiomérov--derivátov kyseliny fenylkarbámovej metódou HPLC.

The chiral stationary phase on the base of beta-cyclodextrin and the mobile phase acetonitrile/0.1 mol/l acetate buffer pH=5.2 (88/12 w/w) were used for the separation of the enantiomers of 1-methoxymethyl, 1-ethoxymethyl, 1-propoxymethyl-2-(1-pyrrolidinyl), (1-piperidino), (1-perhydroazepinyl)ethyl esters of 2-alkoxyphenylcarbamic acid. The influence of the structure of these compounds and the influence of temperature on enantioseparation were studied. The dominant effect on the resolution of enantiomers is exerted by the length of the alkoxysubstituent on the aromatic ring and its position with regard to the stereogenic centre. A decrease in temperature caused an increase in the retention factors of the compounds under study and the resolution values of enantiomers.

Synthesis, pharmacological activity and chromatographic separation of some novel potential beta-blockers of the aryloxyaminopropanol type.

Following our previous structure-activity relationship studies, some novel compounds of the aryloxyaminopropanol type, derived from 2- or 4-hydroxyphenylalkanones, with phenethyl or 3,4-dimethoxyphenethyl groups in the hydrophilic part of the molecule were synthesized and pharmacologically evaluated. The compounds were prepared by means of two methods and their structures were confirmed by the interpretation of their IR, UV and 1H NMR spectra. The enantiomers were separated by HPLC on vancomycin (Chirobiotic V) and teicoplanin (Chirobiotic T) chiral stationary phases. The affinity of the prepared racemic compounds to beta1- and beta2-adrenergic receptors was pre-determined on isolated guinea pig atria and trachea. The assumed cardioselectivity was expressed as the beta1/beta2 ratio. Reciprocal changes in the position of the phenoxysubstituents did not influence the antiisoprenaline activity of the compounds. On the other hand, the increase of the N-substituent size in the hydrophilic part of molecule (3,4-dimethoxyphenethyl moietyled to a substantially higher affinity for cardiac (beta1) than for tracheal (beta2) tissue.

Coupled column chromatography for separation and determination of enantiomers of phenylcarbamic acid derivatives in serum.

Columns packed with vancomycin coupled to an achiral C18 column and beta-cyclodextrin were used for the separation and the determination of enantiomers of alkoxysubstituted esters of phenylcarbamic acid in blood serum. The method involves off-line SPE, the separation of the racemate on a reversed-phase stationary phase, and the separation of the enantiomers on a chiral stationary phase. The limit of detection was 1.0 microg/ml for the vancomycin column and 10.0 microg/ml for the beta-cyclodextrin column in standard solution. In vitro degradation studies of enantiomers demonstrated a difference in the concentation of the enantiomers after the treatment. It was found that the rate constants of R(-)- and S(+)-forms of enantiomers are not significantly different.

In vitro study of enzymatic hydrolysis of diperodon enantiomers in blood serum by two-dimensional LC.

An on-line coupled HPLC system is described for the determination of the enantiomers of diperodon in blood serum. The method involves three steps: (i) off-line preconcentration and clean-up, (ii) separation of the diperodon enantiomers from the matrix components on a reversed-phase stationary phase, and (iii) separation of the racemate from the reversed-phase column on a teicoplanin chiral stationary phase. The method is suitable for simultaneous determination of both enantiomers in serum up to 0.5 microg/ml. The degradation of diperodon enantiomers was studied in serum by an in vitro method and the experimental rate constants were determined. The enantiomeric hydrolysis rates and half-lives for diperodon in serum are different.

[Study of local anesthetics. CLIX. HPLC separation of 1-methyl-2-piperidinoethylesters of alkoxyphenylcarbamic acid]. / Stúdium lokálnych anestetík CLIX. HPLC separácia 1-metyl-2-piperidínoetylesterov kyselín alkoxyfenylkarbámových.

The paper employed beta- and gamma-cyclodextrins as chiral stationary phases in HPLC, the mobile phases being polar organic solvents. Enantiomers of alkoxysubstituted esters of phenylcarbamic acids (local anaesthetics) were separated and various effects on the process of separation were examined. Primarily the effects of the composition and concentration of organic solvents and the effect of the presence of ionic modifiers in the mobile phase were investigated. The conditions of separation of the enantiomers of phenylcarbamic acid derivatives were found. Interactions influencing separation of enantiomers are also discussed.

Study of local anaesthetics, Part 146: Correlation between local anaesthesia, coded structural information, and chromatographic properties for homologous series of alkoxysubstituted esters of phenylcarbamic acid using a neural network.

RP HPLC capacity factors were used for the characterisation of the lipophilicity of homologous series of o- and m- alkoxy-substituted pyrolidino-, piperidino-, and N-methylpiperazino esters of phenylcarbamic acid. The mathematical method of a neural network was employed for supplementing of the incomplete original data matrix and for smoothing the biological data. The dependencies of the number of carbon atoms in the alkoxy side chain (resp. LC capacity factors) on the surface anaesthesia for the homologous series have parabolic character. The surface anaesthetic activity of the o-alkoxy-substituted derivatives was higher than that of m-alkoxy-substituted derivatives. m-Alkoxy-substituted esters presented maxima of activity at 6 and o-derivatives at 7 carbon atoms in the alkoxy side chain.

[Studies of local anesthetics. CL. Models of the dependence of local anesthetic effectiveness of basic esters of alkoxy-substituted phenylcarbamic acids on capacity factor k']. / Stúdium lokálnych anestetík CL. Modely závislosti lokálno-anestetickej úcinnosti bazických esterov alkoxysubstituovaných kyselín fenylkarbámových na kapacitnom faktore k'.

On the basis of proposed six models of the dependence of local anaesthetic effectiveness of series of alkoxysubstituted derivatives of phenylcarbamic acid, this activity was studies in dependence on the capacity factor k' as the parameter of lipophilicity. The most suitable models proved to be y = (Cx + Ci).k' for surface anaesthesia, and y = Cx + Ci log k' for infiltration anaesthesia, y being the value of the decadic logarithm of surface or infiltration local anaesthetic activity, Cx the coefficient characterizing the nitrogenous base, Ci the coefficient characterizing the individual alkoxygroups, and k' the capacity factor from HPLC.

Relationships between the lipophilicity of some 1,4-piperazine derivatives of aryloxyaminopropanols and their beta-andrenolytic activity.

Nineteen 1,4-piperazine derivatives of aryloxyaminopropanol were evaluated with respect to beta-adrenolytic activity. The retention factors obtained from HPLC, RM values obtained from partition TLC and the lipophilic Hansch's (4) constants pi were determined and the compounds were studied with respect to their lipophilicity based on chromatographic properties. The study of the influence of different substituents introduced at the para position on the phenyl ring on the retention factor indicated the log k vs. the number of carbon atoms in R1 substituent to be a linear relationship. Attempts have been made to relate the beta-adrenolytic activity to the lipohydrophilic parameters by deriving a quantitative relationship between them. Significant parabolic correlation was observed between the beta-adrenolytic activity and the logarithm of the retention factor, log k. An analogous relationship was obtained between the beta-adrenolytic activity of the compounds and the RM values obtained from partition TLC as well as Hansch's lipophilic constants pi.