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.

The enantiomers of thirteen 2-, 3-, and 4-alkoxyphenylcarbamic acid 2-methoxy-1-[(4-methylpiperazino)methyl]ethyl ester were separated on a (S,S) Whelk-O 1 CSP column isothermally in the range of 0-50 degrees C at 10 degrees C increments, using methanol/ water (90/10, v/v) containing 17.5 mmol L(-1) acetic acid and 14.36 mmol L(-1) triethylamine as a mobile phase. The dependence of the natural logarithms of retention and selectivity factors (In k, In alpha, respectively) on the inverse of temperature, 1/T, was used to determine thermodynamic data of enantiomers of alkoxysubstituted phenylcarbamic acid 2-methoxy-1-[(4-methylpiperazino) methyl]ethyl esters. Enthalpyentropy compensation plots showed that all of the compounds in this study separate via the same enthalpy-driven chiral recognition mechanism.

The selectivity tuning of two columns coupled in series is investigated in chiral high-performance liquid chromatography. Two columns with reversal enantioselectivities [(R,R) Whelk-O 1 and (S,S) Whelk-O 1] are coupled in series via a T connector. Selectivity of such a column series is tuned by varying the mobile phase flows in the individual columns. The flow ratio necessary for the required selectivity is calculated on the basis of retention factors measured on the individual columns. The performance of this method for adjusting the required selectivity is studied by the separation of enantiomers of alkoxy substituted esters of phenylcarbamic acid. It is demonstrated that the change of the mobile phase flows in the individual columns enables change in the elution order of enantiomers.

& This paper illustrates the composition of propolis samples obtained from two regions in the Slovak Republic and focuses on the determination of coumarins. The HPLC method with on-line spectrophotometric and fluorescent detection was used for the separation and the determination of coumarins from the subgroup of simple coumarins (esculin, daphnetin, fraxetin, umbelliferone, 4-methylumbelliferone, 4-hydroxycoumarin, scoparone, coumarin, herniarin) and cinnamyl alcohol. The results confirmed that the quantity of umbelliferone, 4-methylumbelliferone, and scoparone in the propolis depends on the area of collection. The HPLC results were compared with those obtained by the spectrofluorimetric method developed for the determination of total coumarins (calculated as scoparone). For the quantification of total coumarins in propolis extracts we found 15% higher values of coumarin content by fluorescence spectrometry than by HPLC, which can be ascribed to the higher matrix effects on fluorescence spectra.

A series of 17 halogenides of quaternary ammonium salts of the alkylpiperidinylethyl esters of 2-pentoxy (and 2-heptoxy) substituted phenylcarbamic acids were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, and M. avium. Correlation of this action with lipophilicity (log P, 1-octanol-water system) was used for the description of the structure-antimycobacterial activity relationships (QSARs). The activity increased with the increasing lipophilicity of the compounds.