Forced Degradation Studies of Nateglinide by the First-Order Derivative Spectrophotometric Method and the Density Functional Theory of the Nateglinide Molecule

Nateglinide (NAT) is an oral antihyperglycemic agent used for the treatment of noninsulin-dependent diabetes mellitus. We evaluated the NAT stability under various forced degradation tests (acidic, basic) and predicted the degradation mechanism of the NAT molecule in the gaseous phase and aqueous media. A first-order derivative spectrophotometric method was used for the identification of NAT and the products of its degradation. NAT appeared to be stable in acidic but not in basic media. A probable reaction path of the NAT molecule with OH radicals was analyzed. The optimized geometry was calculated with Gauss View 5. Subsequently, the lowest energy status was determined through geometric optimization using Gaussian 09 software. Aiming to determine the intermediates in the photocatalytic degradation mechanism, the geometric optimization of the molecule was realized using the density functional theory method. The activation energy for the probable reaction path was calculated, and their most stable state from the thermodynamic perspective was determined for the gaseous phase and aqueous media. The predicted mechanism was confirmed by comparison with the experimental results on simple structures reported in the literature.