Indicative stability method by high performance liquid chromatography for analysis of metformin hydrochloride tablets

Abstract

Metformin hydrochloride (MTF) is an oral antidiabetic widely used in the treatment of type II diabetes
mellitus. The present work had as objective to develop a stability-indicating method for analysis of MTF related
substances with adequate selectivity, using high performance liquid chromatography. The proposed method was
carried out in C18 - 4.6 mm x 250 mm - 5μm column, isocratic elution, DAD detector, at wavelength of 218 nm. The
mobile phase consisted of monobasic ammonium phosphate dissolved in ultra-pure water, pH 2.0, flow 0.7 mL / min
and column oven temperature at 30°C. The proposed method was evaluated through the forced degradation study
of the active pharmaceutical ingredient and the formulation, being exposed to acid hydrolysis conditions (1M HCl - 10
days), basic hydrolysis (1M NaOH - 15 hours), neutral hydrolysis 10 days), oxidation (30% H2O2 - 5 days), photolysis (6
x 106 lux / hour), temperature (70°C - 10 days), metal ions (Copper Chloride II 1 M - 24 hours), humidity (60°C / 75%
RH - 10 days). Degradation was found in the oxidative condition (26.6% in the formulation and 16.4% in the API) and
in the basic hydrolysis (10.0% in the API). The method was able to detect the possible products of degradation of the
formulation, being specific and able to measure the content of the active pharmaceutical ingredient in the presence of
degradation products without interference, being considered a stability-indicating method.