This work aimed to develop a chiral separation method of ketoconazole enantiomers using electrokinetic chromatography. The separation was achieved using heptakis (2, 3, 6-tri-O-methyl)-β-cyclodextrin (TMβCD), a commonly used chiral selector (CS), as it is relatively inexpensive and has a low UV absorbance in addition to an anionic surfactant, sodium dodecyl sulfate (SDS). The influence of TMβCD concentration, phosphate buffer concentration, SDS concentration, buffer pH, and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 2.5 containing 20 mM TMβCD, 5 mM SDS, and 1.0% (v/v) methanol with an applied voltage of 25 kV at 25 °C with a 5-s injection time (hydrodynamic injection). The four ketoconazole stereoisomers were successfully resolved for the first time within 17 min (total analysis time was 28 min including capillary conditioning). The migration time precision of this method was examined to give repeatability and reproducibility with RSDs ≤5.80% (n =3) and RSDs ≤8.88% (n =9), respectively.

A molecular docking study, using molecular mechanics calculations with AutoDock and semi-empirical PM3 calculations, was used to predict the enantiodiscrimination of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) and ketoconazole (KTZ) enantiomers. A Density Functional Theory (DFT) single-point calculation at the level of B3LYP/6-311G (d,p) was performed for the PM3-optimized complexes to obtain more accurate binding energy and the electronic structures of the complexes. The difference in energies of the inclusion complexes between the KTZ enantiomers and TMβCD is probably a measure of chiral discrimination, which results in the separation of the enantiomers as observed in the experimental studies.

Capillary electrokinetic chromatography (EKC) has been established as a versatile and robust capillary electrophoresis (CE) method for the separation of enantiomers. One of the most attractive advantages of EKC for the separation of enantiomers is its ease of change of separation media in method development. The separation solution can easily be altered to find the optimum separation media and one can also use an expensive chiral selector because small amounts of it are required. This work aims to develop experimental and theoretical analysis of the chiral separation of ketoconazole using EKC and molecular modelling study, respectively. In the first part of the study, several cyclodextrins (CD) as the chiral selectors (CS) namely α-cyclodextrin, sulfated β-cyclodextrin, (2-hydroxylpropyl)-β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin, and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin were screened. CDs were initially chosen as they are easily available and cheap. Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) exhibited a higher enantioselectivity power compared with other tested CDs. The influence of TMβCD concentration, buffer pH, buffer concentration, separation temperature and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 3.0 containing 20 mM TMβCD with an applied voltage of 30 kV at 35°C with 5 s injection time (hydrodynamic injection). The ketoconazole enantiomers were resolved in less than 10 min (Rs 1.79). In order to understand possible chiral recognition mechanisms of ketoconazole with TMβCD, host-guest binding procedures of TMβCD and ketoconazole were studied using the semi-empirical PM3 calculations.________________________________________GRAPHICAL ABSTRACT

Water can be an irritant to a power transformer, as it is recognized as a major hazard to the operation of transformers. The water content of a transformer insulation system comprises the water in the transformer insulation oil and in the cellulose paper. The increase in the water content in the insulation system leads to reduced breakdown voltage, accelerated aging of the oil–paper insulation system, and the possibility of producing bubbles at high temperatures. Therefore, various techniques have been applied to measure the water content in both oil and paper insulation. This article comprehensively reviews and analyzes the methods (technically or nontechnically) that have been used to monitor the water content in transformer insulation systems. Apart from discussing the advantages and major drawbacks of these methods, the accuracy, measurement time, and cost of each technique are also elucidated in this review. This review can be extremely useful to the utility in monitoring and maintaining the good condition of transformers. Based on the reviewed methods and their challenges, a few future research directions and prospects for determining the water content in transformer insulation systems are outlined, such as utilizing artificial intelligence and enhancing current techniques.