Evaluation of the interaction between sitagliptin and cyclodextrin derivatives by capillary electrophoresis and nuclear magnetic resonance spectroscopy

Tamás Sohajda, Wen Hui Hu, Li Li Zeng, Hong Li, Lajos Szente, B. Noszál, S. Béni

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 (15min) with optimized parameters (10°C, pH=4.4, 40mM 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 1H and 19F NMR experiments and resulted in a 1:1 complex. The structure of the inclusion complex was elucidated using 2-D ROESY NMR experiments.

Original languageEnglish
Pages (from-to)2648-2654
Number of pages7
JournalElectrophoresis
Volume32
Issue number19
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Capillary electrophoresis
Cyclodextrins
Capillary Electrophoresis
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Enantiomers
Titration
Stoichiometry
Buffers
Substitution reactions
Experiments
Phosphates
Temperature
Acids
Sitagliptin Phosphate
Pharmaceutical Preparations

Keywords

  • F NMR
  • Dual cyclodextrin
  • Enantioseparation
  • Januvia
  • Sitagliptin synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Evaluation of the interaction between sitagliptin and cyclodextrin derivatives by capillary electrophoresis and nuclear magnetic resonance spectroscopy. / Sohajda, Tamás; Hu, Wen Hui; Zeng, Li Li; Li, Hong; Szente, Lajos; Noszál, B.; Béni, S.

In: Electrophoresis, Vol. 32, No. 19, 10.2011, p. 2648-2654.

Research output: Contribution to journalArticle

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