Enhanced detection for determination of enantiomeric purity of novel agomelatine analogs by EKC using single and dual cyclodextrin systems.

Performing CD-EKC, baseline separation of five agomelatine analogs, potential antidepressant compounds, was achieved. A method for the enantioresolution and determination of enantiomeric purity of these naphthalene derivatives was developed using capillaries dynamically coated with polyethylene oxide and anionic cyclodextrins (highly sulfated CD) as chiral selectors. Operational parameters such as the nature and concentration of the cyclodextrins were investigated. In a second step the implementation of a dual cyclodextrin system was found to strongly enhance the LOD of the analytes. After optimization, best conditions were a 25 mM phosphate buffer at pH 2.5 containing 5% w/v (i.e. 19.7 mM) of highly sulfated-γ-CD and 10 mM of 6-monodeoxy-6-monoamino-β-CD dual system, leading to resolution of, at least, 3.6 in 35 min. A preliminary validation of the developed method was undertaken: linearity, precision, and LOD and LOQ were evaluated. The latest ones were found equal to 0.25 and 0.82 μM and to 0.31 and 0.96 μM respectively for the first and the second enantiomer of compound 1.