Enhanced detection for determination of enantiomeric purity of novel agomelatine analogs byEKCusing single and dual cyclodextrin systems

Abstract

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.

Evaluation and comparison of three different separation techniques for analysis of retroamide enantiomers and their biological evaluation against h-P2X7 receptor

“…To save time and with regard to very recent works [30][31][32], the cationic MM-␤-CD was firstly tested, added to the initial 15 mM of SBE-␤-CD. An equimolar dual system was constituted containing 15 mM of MM-␤-CD and 15 mM of SBE-␤-CD.…”

Separations of antifungal compounds in capillary electrophoresis with two anionic cyclodextrins

“…As previously stated, the conditions tested were the following: a BGE consisting of 25 mM phosphate buffer at pH 2.5 in a fused‐silica capillary coated with PEO. Despite of their high cost, the good enantioseparation abilities of highly sulfated CDs have been demonstrated in numerous previous papers to cite only few, including for neutral pharmaceutical compounds . HS‐γ‐CDs in solution were then tested and were prepared at ca.2 mM (0.5% w/v), ca.4 mM (1% w/v), ca.16 mM (4% w/v), ca.20 mM (5% w/v) and ca.24 mM (6% w/v) in a pH 2.5 phosphate buffer 25 mM.…”

Chiral selectors in CE: Recent development and applications (mid‐2014 to mid‐2016)

“…Dual‐CD systems were also used for enhanced detection and determination of the enantiomeric purity of agomelatine analogues (five naphthalene derivatives) . Despite the very good enantioselectivity of ΗS‐γ‐CD toward the five naphthalene derivatives, the migration times were too long, the efficiency was poor ( N ∼ 12 000–16 000) and the sensitivity was not satisfactory (LOD = 10.8 μM, LOQ = 35.7 μΜ for the first enantiomer of naphthalene derivative compound 1).…”