Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization

Chirality is a property of asymmetry which determines the pharmacokinetic and pharmacological profiles of optically active pharmaceuticals. Verapamil (VER), a calcium channel blocker phenylalkylamine derivative used in the treatment of cardio-vascular diseases, is a chiral compound, marketed as a racemate, although differences between the pharmacokinetic and pharmacological attributes of the enantiomers have been reported. The aim of our study was to develop a new chiral separation method for VER enantiomers by capillary electrophoresis (CE) using cyclodextrins (CDs) as chiral selectors (CSs). After an initial screening, using different native and derivatized CDs, at four pH levels, heptakis 2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was identified as the optimum CS. For method optimization, a preliminary univariate approach was applied to characterize the influence of analytical parameters on the separation followed by a Box–Behnken experimental design to establish the optimal separation conditions. Chiral separation of enantiomers was achieved with a resolution of 1.58 in approximately 4 min; the migration order was R-VER followed by S-VER. The method analytical performance was evaluated in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burnam experimental design). The developed method was applied for the determination of VER enantiomers in pharmaceuticals. Finally, a computer modelling of VER–CD complexes was used to describe host–guest chiral recognition.

Mining Method Optimization of Gently Inclined and Soft Broken Complex Ore Body Based on AHP and TOPSIS: Taking Miao-Ling Gold Mine of China as an Example

The gently inclined thin to medium thickness ore body under a weak rock stratum is one of the typical difficult bodies to mine. In order to solve the fuzziness, randomness, and uncertainty in the process of mining method optimization for such ore bodies, a multi-level, multi-factor, multi-objective, and multi-index comprehensive evaluation system involving technology, economy, construction, and safety was constructed by combining the analytic hierarchy process (AHP) and technique for order preference by similarity to ideal solution (TOPSIS). Taking the Miao-ling gold mine in China as an example, the AHP-TOPSIS comprehensive decision model of mining method optimization is established, the comprehensive superiority degrees of the four mining schemes are 67.57%, 45.07%, 56.07%, and 31.63%, and the upward horizontal drift backfill mining method is determined as the optimal scheme. The method is verified in the actual production of the mine, which not only ensures the safe production of the mine, but also achieves better technical and economic effects. The research results provide a reference for the optimization of mining methods for gently inclined and soft broken complex ore bodies at home and abroad.