Study of forced degradation behavior of Eletriptan hydrobromide by LC and LC-MS and development of stability-indicating method

Abstract

The objective of the present study was to report the stability profile of novel antimigrain drug Eletriptan hydrobromide based on the information obtained from forced degradation studies. The drug was subjected to acid (0.1-1 mol L-1 HCl), neutral and base (0.1-1 mol L-1 NaOH) hydrolysis and to oxidative decomposition (3-15% (v/v) H2O2). Photolysis and thermo degradation at 75 °C were carried out in methanol solution and in solid state with both Eletriptan hydrobromide bulk drug and the tablet formulation. The products formed under different stress conditions were investigated by LC and LC-MS. The experimental conditions for LC were chosen by employing experimental design and multicriteria decision making methodology. These powerful tools enabled the accomplishment of satisfactory resolution with the shortest possible analysis time. Analytes were separated on a C18 column (XTerra™, 150 mm × 3.9 mm, 5 μm) with the mobile phase composed of methanol-water solution of TEA (pH 6.52, 1%, v/v) (30:70, v/v) pumped at 1 mL min-1 flow rate. The column temperature was set at 50 °C and the detection at 225 nm using DAD detector. The LC method was suitably modified for LC-MS analysis which was further used to characterize the arisen degradation products. The possible degradation pathway was outlined based on the results. The drug appeared to be instable towards every stress condition but oxidation. The stability was not jeopardized even under more exaggerated conditions such as increased temperature of the solutions to 75 °C, increased strength of acid/alkali solutions and prolonged testing period. Validation of the LC-DAD method was carried out in accordance with ICH guideline. The method met all required criteria and was applied when testing the commercially available tablets.