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

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 (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.

Development and validation of a cyclodextrin‐modified capillary electrophoresis method for the enantiomeric separation of vildagliptin enantiomers

“…A factorial analysis study was performed by orthogonal experimental design in which several factors are varied at the same time to optimize the separation method . The orthogonal experimental design techniques are widely applied in the state of art method and process developments in the pharmaceutical industry as they provide more information from less experiments than the “one factor at a time” approach in which each factor is varied in turn while the others remain constant . Six experimental factors (each tested at three levels) were chosen as variable parameters: applied temperature and voltage, chiral selector and BGE concentrations, pH, and the parameters of the hydrodynamic injection.…”

“…To the best of our knowledge, no chiral method has been published so far on Vilda enantioseparation, only non‐chiral quantitative determinations in bulk and pharmaceutical formulations were reported . CD‐based chiral analysis of other DPP‐4 inhibitors, such as alogliptin and sitagliptin , has already been published by our group. However, the “gliptins” represent a new class of oral antihyperglycemic agents, they are structurally very divers, so there is no general chiral separation method that may be applied to analyze all kinds of “gliptin enantiomers,” each derivate has a tailor made method.…”

Quantitation of Sitagliptin in Drug Product by Validated Reversed Phase Liquid Chromatographic Technique

“…25 However, UV spectrophotometry is the simplest technique but it is deficient in accuracy and precision and needs relatively higher amount of analytes for detection. HPLC is the best option for analysis because of its simplicity and sensitivity.…”

Evaluation of Process Impurities and Degradants of Sitagliptin Phosphate by Validated Stability Indicating RP-LC Method

“…Two studies were discussed about simultaneous determination of sitagliptin with simvastatin [5] and with metformin [6] from oral dosage-tablet forms. Bioanalytical studies like simultaneous quantitation of metformin and sitagliptin from mouse and human dried blood spots using LDTD-MS [7] and evaluation of the interaction between sitagliptin and cyclodextrin derivatives by CE-NMR [8] and other studies like determination of sitagliptin in human urine…”