HPLC Enantioseparation of Phenylcarbamic Acid Derivatives by Using Macrocyclic Chiral Stationary Phases

The HPLC by using chiral stationary phases based on macrocyclic antibiotics, dimethylphenyl carbamate cyklofructan 7 and β-cyclodextrin in terms of polar-organic separation mode (mobile phase methanol/acetonitrile/acetic acid/triethylamine) were used for enantioseparation of alkoxy derivatives of phenylcarbamic acid. The effect of the analyte structures on the efficiency of enantioseparation was investigated. The most suitable stationary phase was teicoplanin aglycone, where the separations of the enantiomers were obtained (the resolution value from 0.65 to 2.90, depending on the structure of the analyte). Significant effect on the resolution of the enantiomers has position of alkoxy substituent in the hydrophobic part of the molecule. The enantiorecognition was achieved for 3-alkoxysubstituted derivatives

HPLC separation and determination of dicoumarol and other simple coumarins in sweet clover

Dicoumarol is a mycotoxin, that acts as a blood anticoagulant, is formed during the microbial action of molds and fungi in spoiled hay or silage containing high-coumarin plant. A HPLC-DAD method for determination of coumarins, including dicoumarol, coumarin, and 4-hydroxycoumarin was developed. Methanol and acetic acid were used as mobile phase with gradient elution. The simultaneous separation was performed using C18 type of stationary phase. The recoveries were 88.6 – 92.6 %, 91.8 – 95.0 %, and 89.7 – 94.1 % (evaluated for three concentration levels) for dicoumarol, coumarin, and 4-hydroxycoumarin respectively. The parameters of system suitability (repeatability of retention times and peak areas) were determined for evaluation of the method. The method showed a good linearity in the concentration range 0.7 – 100 μg.mL−1 for dicoumarol, 0.05 – 100 μg.mL−1 for coumarin and 4-hydroxycoumarin with correlation coefficients higher than 0.9885. Extracts of sweet clover herb, hay, and spoiled hay were subjected to HPLC-DAD analysis. The most abundant compound in sweet clover herb and hay extracts was coumarin. In spoiled sweet clover hay extract the 4-hydroxycoumarin was detected in addition. The formation of 4-hydroxycoumarin was also observed in the synchronous fluorescence spectra recorded at the wavelength difference of 90 nm (difference between emission and excitation wavelength)

Study of Local Anaesthetics. Part 172* Comparison of the Influence of Auxilliary Substances on Physicochemical Parameters of Two Phenylcarbamic Acid Derivatives

It this work was studied the influence of polyols (propylene glycol, glycerol and sorbitol) on the physicochemical parameters (partition coefficient and surface tension) and liberation from aqueous solutions with propylene glycol of two derivatives of phenylcarbamic acid. Studied parameters and liberation were influenced by the structure of the studied derivatives and with the type and concentration of polyols

Synthesis, physico-chemical properties and bioloclical activitv of 1-(4-fluorophenvl)-4-[3-(2-,3- and 4-alkyloxyphenylcarbamoyloxy)-2-hydroxypropyl] piperaziniumchlorides

1-(4-fluoropheny1)-4-[3-(2-,3- and 4-alkyloxyphenylcarbamoyloxy)-2-hydroxypropyl]piperaziniumchlorides, with one to four carbon atoms in the alkoxy group on aromatic ring have been synthesized as the derivatives of substituted phenylcarbamic acid. The structures were confirmed by their spectral data. Potential antiarrhythmic activity was evaluated in guinea-pigs model. Preliminary studies demonstrated that the evaluated compounds, using ouabain arrhythmia model, appear to possess only moderate antiarrhythmic activity. Only compound marked as 4f appears to be more potent and lead us to focus our attention on structures with more bulky substituent in the m-position at aromatic ring in the hydrophilic part of molecule

Chiral Aspects of Local Anesthetics

Thanks to the progress made in chemical technology (particularly in the methodologies of stereoselective syntheses and analyses) along with regulatory measures, the number of new chiral drugs registered in the form of pure enantiomers has increased over the past decade. In addition, the pharmacological and pharmacokinetic properties of the individual enantiomers of already-introduced racemic drugs are being re-examined. The use of the pure enantiomer of a drug that has been used to date in the form of a racemate is called a “chiral switch”. A re-examination of the properties of the pure enantiomers of racemates has taken place for local anesthetics, which represent a group of drugs which have long been used. Differences in (R) and (S)-enantiomers were found in terms of pharmacodynamic and pharmacokinetic activity as well as in toxicity. Levobupivacaine and robivacaine were introduced into practice as pure (S)-(−)-enantiomers, exhibiting more favorable properties than their (R)-(+)-stereoisomers or racemates. This overview focuses on the influence of chirality on the pharmacological and toxicological activity of local anesthetics as well as on individual HPLC and capillary electrophoresis (CE) methods used for enantioseparation and the pharmacokinetic study of individual local anesthetics with a chiral center

Determination of Critical Micellar Concentration of Homologous 2-Alkoxyphenylcarbamoyloxyethyl-Morpholinium Chlorides

The critical micellar concentrations of selected alkyloxy homologues of local anesthetic 4-(2-{[(2-alkoxyphenyl)carbamoyl]oxy}ethyl)morpholin-4-ium chloride with nc = 2, 4, 5, 6, 7, 8, and 9 carbons in alkyloxy tail were determined by absorption spectroscopy in the UV–vis spectral region with the use of a pyrene probe. Within the homologous series of the studied amphiphilic compounds, the ln(cmc) was observed to be dependent linearly on the number of carbon atoms nc in the hydrophobic tail: ln(cmc) = 0.705–0.966 nc. The Gibbs free energy, necessary for the transfer of the methylene group of the alkoxy chain from the water phase into the inner part of the micelle at the temperature of 25 °C and pH ≈ 4.5–5.0, was found to be −2.39 kJ/mol. The experimentally determined cmc values showed good correlations with the predicted values of the bulkiness of the alkoxy tail expressed as the molar volume of substituent R, as well as with the surface tension of the compounds