A capillary electrophoresis method for the determination of the linagliptin enantiomeric impurity

Abstract

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.

Application of experimental design in HPLC method optimization and robustness for the simultaneous determination of canagliflozin, empagliflozin, linagliptin, and metformin in tablet

“…LIG was investigated using spectrophotometric and chromatographic methods in pure form, in pharmaceutical dosage form, and in biological fluids (Mai et al, 2020;Nannapaneni et al, 2016). On the contrary, several analytical methods based on spectrophotometry (Abdel-Ghany et al, 2017;Moussa et al, 2018) and chromatography (Abdel-Ghany et al, 2016;Ayoub, 2015;Bhole et al, 2017;Dayyih et al, 2021;EL Sheikh et al, 2020;Naazneen & Sridevi, 2016;Raut et al, 2020;Rizk et al, 2021) were described for the simultaneous determination of LIG and EMG.…”

Enantioseparation of basic drugs by reverse phase high‐performance liquid chromatography system using carboxymethyl‐β‐cyclodextrin as chiral mobile phase additive

“…38 Moreover, the anionic β-CD derivatives have been widely explored in the separation of basic chiral compounds containing amino groups, due to the electrostatic interactions, besides the hydrophobic inclusions, which enhanced the stability of compounds-CD inclusions. In recent years, CM-β-CD has been frequently utilized as a chiral selector to separate enantiomeric compounds by capillary electrophoresis (CE) 25,[39][40][41][42] but relatively few in HPLC. 37,43,44 In this work, the enantioseparation of six basic drugs (α-phenylethylamine…”

Determination of enantiomeric impurity of tenofovir disoproxil fumarate on a cellulose tris(3,5‐dichlorophenyl‐carbamate) chiral stationary phase and the characterization of its related substances

“…This issue can be resolved by employing a design of experiments (DoE) approach for systematic method development. The DoE approach contributes to reducing the number of experiments and fixing critical and unpredictable errors [8,[12][13][14].…”