Linagliptin is a highly specific, long-acting inhibitor that is used as an orally administrable agent for type-2 diabetes treatment. Because only the R-enantiomer is of clinical use, we developed a capillary electrophoresis method for the determination of the enantiomeric impurity of this compound. Carboxymethyl-β-cyclodextrin was selected as the chiral selector for the separation of linagliptin enantiomers. Design of experiments and desirability functions were used for the analytical optimization, which was focused on understanding and improving the electrophoretic process. The effects of significant parameters (background electrolyte concentration and pH, cyclodextrin concentration, temperature, and voltage) were thoroughly investigated. The complete separation of linagliptin and its enantiomeric impurity with baseline resolution was achieved within 10 min on an uncoated fused-silica capillary (50 μm inner diameter, 365 μm outer diameter, 64.5/56 cm in total/ effective length) maintained at 25 • C, under an applied voltage of 28.0 kV. The background electrolyte contained 70 mM sodium acetate and 4.7 mM carboxymethyl-β-cyclodextrin, and the pH was adjusted to 6.10. The method was validated, and a limit of quantitation of 0.05% for the impurity was estimated.

A simple, cost-effective, and greener HPLC method was investigated to determine 14 β-lactams. To achieve this, various strategies were implemented such as the use of an aqueous mobile phase, ionic liquids, or an alternative organic solvent. Preliminary experiments were conducted using "one-factor-at-atime" to identify the significant factors affecting chromatographic performance. The experimental design (central composite design) was then applied to thoroughly examine the effects of the key factors and exploit them to achieve optimal HPLC condition. The developed method was less hazardous and improved the retention and peak shape, compared with other conventional methods. The optimized assay condition was validated according to the ICH guidelines and effectively applied for the quantification of some β-lactams in various formulations. These results imply that this novel HPLC method can be employed for routine analyses of some β-lactams in pure drug and commercial formulations.