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Oxazepam undergoes reversible enantiomerization at ambient temperature. Standard solutions of this compound and extracts from tablets (both with c=0.1 mg/mL) were injected on a chiral HPLC column (Chirobiotic T) at various temperatures (273 K‐313 K, increment 5 K). The mobile phase with the composition MeOH/TEA/Hac (100/0, 1/0, 1) and flow rate 1.0 mL/min were used.1 Both the separation and the interconverson process occurred simultaneously. The various profiles obtained by a UV detector included two peaks (unreacted zone) and a plateau sandwiched between two peaks (reacted zone). These profiles could be explained by on‐column enantiomerization. The unreacted molecule zone on the profile was fused with the reacted molecule zone. The computer assisted peak deconvolution procedure (Origin 7.0 section peak fitting) was used for the determination of peak areas in peak clusters. The deconvolution of experimentally obtained chromatograms enabled the resolved and determined areas of each zones. As follows, the peak areas were used for calculation of thermodynamic parameters of enantiomerization – apparent rate constants (k1app and k-1app), Gibbs free energy (ΔG1app, ΔG-1app), enthalpy (ΔH1app, ΔH-1app), and entropy (ΔS1app, ΔS-1app). [ABSTRACT FROM AUTHOR]

The dynamic HPLC was performed with the goal to estimate the influences on the configurational stability of diazepam conformers in chiral environment. The effect of sample solvent, temperature, flow rate, and pH of mobile phase on behaviour of diazepam conformers during their separation on chiral β‐cyclodextrin was studied. The separation of diazepam conformers was complicated due to simultaneous interconversion, which was the result of configurational instability of the diazepam molecule. A statistical approach was used for evaluation of the influence of individual chromatographic parameters on behaviour of diazepam in a given chiral environment. The Principal Component Analysis (PCA) and Cluster Analysis (CA) were applied for accurate interpretation of obtained results. [ABSTRACT FROM AUTHOR]

The HPLC analysis of diazepam conformers was carried out in the temperature range 273–313 K, increment 10 K. The pH of the mobile phase was 3.3; 5.5; 5.5 (I c =const; 6.5; 6.5 I c =const.). The various flow rates of 0.2; 0.5; 1.0; mL/min were used. Chiral stationary phase based on ß-cyclodextrin (ChiraDex) was used for separation of diazepam. The influence of temperature, flow rate, pH of mobile phase, and ionic strength on the retention and elution profile on two peaks of diazepam conformers were studied. After that, the chiral ß-cyclodextrin (0.001 mol/L; 0.003 mol/L; 0.005 mol/L) was added into the mobile phase. The increasing amount of ß-cyclodextrin in the mobile phase caused the disappearance of the first peak. The complete chiral separation of diazepam was not possible because of simultaneous interconversion. The plateau between two peaks of diazepam appeared in the whole range studied, any inhibitory effects of chromatographic conditions (pH of mobile phase, temperature, flow rate, ionic strength) on interconversion was not observed, only the change of the area ratio between two peaks appeared. Off-line standard 1 H and COSY NMR experiments were used to study the diazepam structure in the achiral mobile phase. The results of 1 H and COSY NMR experiments confirmed that there is no pH dependent open-ring reaction of 1,4-benzodiazepine ring that could occur during the residence time of diazepam in the achiral mobile phase. [ABSTRACT FROM AUTHOR]

It has been found that the teicoplanin aglycone (CHIROBIOTIC TAG) chiral stationary phase is a useful column for the high performance liquid chromatographic (HPLC) separation of enantiomers of 1-methyl-2-piperidinoethylesters of 2-, 3- and 4-alkoxy-phenylcarbamic acid (potential local anaesthetic drugs) in the polar organic mode. The enantiomers were separated on a CHIROBIOTIC TAG column, isothermally in the range of 0–50°C with 10°C increments, using methanol [100 mL (v)] containing 17.5 mmol L−1 acetic acid and 4.8 mmol L−1 diethylamine as a mobile phase. van't Hoff plots (dependence of ln ki on 1/T, where k is the retention factor of a solute i and T is the temperature) were linear in the studied temperature interval. This allowed the determination of interaction enthalpies (ΔHi), entropy (ΔSi), and Gibbs energies (ΔGi). This thermodynamic information was used to evaluate the retention and resolution of enantiomers of studied analytes in this HPLC system. [ABSTRACT FROM AUTHOR]