Identification and Structure Elucidation of Forced Degradation Products of the Novel Propionic acid Derivative Loxoprofen: Development of Stability-Indicating Chromatographic Methods Validated as per ICH Guidelines

Abstract

Loxoprofen sodium (LOX) is a recently developed novel propionic acid derivative. Owing to its instability under both hydrolytic and oxidative conditions, the development of simple, rapid and sensitive methods for its determination in the presence of its possible forced degradation products becomes essential. Two simple chromatographic methods, high-performance thin layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC), were developed associated with ultraviolet (UV) detection. In HPTLC-densitometric method, the separation of LOX from its degradation products was achieved using silica gel F254 plates and toluene:acetone:acetic acid (1.8:1.0:0.1, v/v/v) as the developing system followed by densitometric scanning at 220 nm. In the HPLC-UV method, the separation was performed using isocratic elution system with acetonitrile: 0.15% triethylamine (pH 2.2) (50:50, v/v) on C18 analytical column. The flow rate was optimized at 1.0 mL·min-1 and UV detection was achieved at 220 nm. Validation was performed in accordance with the International Conference on Harmonization guidelines and the method was perfectly applied for determination of LOX in its pharmaceutical preparation. The results obtained were statistically compared to those obtained after application of the official HPLC method, where no significant difference was found incompliance with precision and accuracy. Identification and characterization of the possible hydrolytic degradation product under alkaline conditions and that produced during oxidative degradation using hydrogen peroxide were structurally elucidated using infrared and mass spectrometry analyses.

Protective Effect of Selected Antioxidants on Naproxen Photodegradation in Aqueous Media

“…It is reported that the biological effects of some pharmaceuticals are changed by UV irradiation [6,7,8] on account of their photoconversion to photoproducts. Various photochemical reactions may be induced by UV irradiation [9,10,11]. These reports indicate that the generation of various photoproducts is dependent on these chemical reactions.…”

“…Furthermore, additional research showed that the oxidation of the dihydropyridine ring following the generation of pyridine derivatives was the main degradation mechanism [7,13,14]. There are some reports showing the more complex photochemical reaction of nifedipine with the formation of further photoproducts [10,15,16]. Moreover, photoproducts of dihydropyridine have no therapeutic effects [7,8].…”