Analysis of Nefopam by TLC-densitometry. A Study of Degradation Mechanism in Solutions Under Stress Conditions

摘要

A new, simple, selective, precise and accurate thin-layer chromatographic method for quantification of nefopam hydrochloride in formulations has been established and validated. TLC F_(254) silica gel plates in combination with a mixture of chloroform : methanol: glacial acetic acid (9 : 2 : 0.1, v/v/v) as mobile phase were used. UV detection was performed densitometrically at a wavelength of 222 nm. The method was validated for linearity, precision, accuracy, selectivity and specificity in accordance with ICH guidelines. Nefopam hydrochloride was subjected to acid and alkaline hydrolysis at different temperatures. The degradation products were well resolved from the pure drug with substantially different R_F values and absorption spectra. LC-MS/MS analysis was used to characterize the chemical properties of degradation products. The likely chemical structures of the major degradation products are 2-[(2-benzyl-benzyl)(methyl)amino]ethanol, 2-[{2-[hydroxyl(phenyl)methyl]-benzyl}(methyl)-amino] ethanol and diphenylmetha-none.