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Evaluation of the interaction between sitagliptin and cyclodextrin derivatives by capillary electrophoresis and nuclear magnetic resonance spectroscopy
Author(s) -
Sohajda Tamás,
Hu Wen Hui,
Zeng Li Li,
Li Hong,
Szente Lajos,
Noszál Béla,
Béni Szabolcs
Publication year - 2011
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201000639
Subject(s) - cyclodextrin , chemistry , capillary electrophoresis , enantiomer , titration , analyte , nuclear magnetic resonance spectroscopy , aqueous solution , chromatography , analytical chemistry (journal) , capillary action , stability constants of complexes , stereochemistry , materials science , composite material
An aqueous capillary electrophoretic method was developed for chiral analysis of the novel anti‐diabetic drug, sitagliptin. The acid–base profiling of the analyte was carried out using both capillary electrophoresis and nuclear magnetic resonance pH titrations. The apparent complex stability and chiral separation properties were investigated with 30 different cyclodextrins under acidic conditions. The effect of concentration and pH of the BGE, temperature of the capillary, and the type and concentration of the chiral selector on the enantiomer resolution were thoroughly investigated. The effects of dual cyclodextrin systems on separation were also extensively studied. Complete separation of racemic sitagliptin with good resolution ( R S =2.24) was achieved within a short time (15 min) with optimized parameters (10°C, pH=4.4, 40 mM phosphate buffer) of a sulfobutylether‐β‐cyclodextrin (averaged degree of substitution ∼4) and native β‐cyclodextrin dual system. The averaged stoichiometry of the inclusion complex was determined using the Job plot method with both 1 H and 19 F NMR experiments and resulted in a 1:1 complex. The structure of the inclusion complex was elucidated using 2‐D ROESY NMR experiments.