Analytical Separation of Closantel Enantiomers by HPLC

Abstract

Closantel is an antiparasitic drug marketed in a racemic form with one chiral center. It is meaningful to develop a method for separating and analyzing the closantel enantiomers. In this work, two enantiomeric separation methods of closantel were explored by normal-phase high-performance liquid chromatography. The influences of the chiral stationary phase (CSP) structure, the mobile phase composition, the nature and proportion of different mobile phase modifiers (alcohols and acids), and the column temperature on the enantiomeric separation of closantel were investigated in detail. The two enantiomers were successfully separated on the novel CSP of isopropyl derivatives of cyclofructan 6 and n-hexane-isopropanol-trifluoroacetic acid (97:3:0.1, v/v/v) as a mobile phase with a resolution (Rs) of about 2.48. The enantiomers were also well separated on the CSP of tris-carbamates of amylose with a higher Rs (about 3.79) when a mixture of n-hexane-isopropanol-trifluoroacetic acid (55:45:0.1, v/v/v) was used as mobile phase. Thus, the proposed separation methods can facilitate molecular pharmacological and biological research on closantel and its enantiomers.

Synergistic antibacterial effects of closantel and its enantiomers in combination with colistin against multidrug resistant gram-negative bacteria

“…Based on the above-mentioned research on chiral drugs and previous studies on CLO enantiomers in our laboratory (Saleh et al, 2021), the in vitro antibacterial activity of CLO, R-CLO, and S-CLO either alone or in combination with CST was systematically evaluated by combined antibacterial, growth inhibition assay, and time-killing curves against both CST-susceptible and insensitive GNB in the present study. On one hand, the current study helps us better understand the mechanism by which CLO works; on the other hand, this difference in stereoselectivity of CLO helps us better develop new drugs and reduce toxic effect, thereby provide more possibilities for its clinic use (Figure 1).…”