ABSTRACT
Imazamox (IMX), a chiral herbicide used in cereals and oilseed crops to control weeds, is commonly sold as a racemic mixture. Its enantiomers, being chiral compounds, may exhibit unique properties when exposed to chiral environments. While IMX enantiomers have been reported to degrade differently in soil and be toxic to some species, their effects on human systems remain poorly understood. This study utilized Caco-2 (human colon adenocarcinoma cell line) cells to assess the in vitro permeability of a racemic mixture of IMX and its isolated enantiomers. Additionally, the study aimed to evaluate whether the metabolite imazamox-O-desmethyl (IMX-D) forms during the permeability process. An enantioselective chromatographic method was developed, fully validated, and the apparent permeability values were obtained. The apparent permeability of rac-IMX, (+)-IMX, and (-)-IMX was determined to be 4.15 × 10-5 , 5.78 × 10-5 , and 7.33 × 10-5 cm s-1 , respectively. These findings suggest that IMX exhibits high intestinal permeability, with an enantioselective absorption for (-)-IMX as compared to (+)-IMX. Finally, the permeability study in Caco-2 cells revealed that the metabolite IMX-D was not generated.
ABSTRACT
Enantioresolution processes are vital tools for investigating the enantioselectivities of chiral compounds. An analyst resolves to optimize enantioresolution conditions once they are determined. Generally, optimization is conducted by a one-factor-at-a-time (OFAT) approach. Although this approach may determine an adequate condition for the method, it does not often allow the estimation of the real optimum condition. Experimental designs are conducive for the optimization of enantioresolution methods via capillary electromigration techniques (CETs). They can efficiently extract information from the behavior of a method and enable the estimation of the real optimum condition. Furthermore, the application of the analytical quality by design (AQbD) approach to the development of CET-based enantioselective methods is a trend. This article (i) offers an overview of the application of experimental designs to the development of enantioselective methods from 2015 to mid-2020, (ii) reveals the experimental designs that are presently employed in CET-based enantioresolutions, and (iii) offers a critical point of view on how the different experimental designs can aid the optimization of enantioresolution processes by considering the method parameters.
