| Popis: |
A sensitive, precise, specific, linear and stability indicating isocratic UPLC-MS/MS method was developed for the analysis of vorpaxar as per ICH guidelines Q1A (R2). Various forced degradation studies were conducted to establish an impurity profile for vorpaxar. Degradation products were produced upon exposing vorpaxar to different degradation conditions (acidic, basic, oxidative, photolytic, aqueous and thermal); the chromatographic separation was achieved with 5mM Ammonium Format Buffer (pH: 4.0): Methanol: Acetonitrile, (40:30:30, % v/v) using the Pursuit XRs-100Å, C18, 4.6 x 50 mm, 10 µm analytical column. The total analysis time was 3.5 min and flow rate was set to 0.2 ml/min. The mass transitions of vorapaxar and vorapaxar-D5 obtained were m/z 591.4/447.2 and 498.6/447.2. The standard curve shows correlation coefficient (r2) greater than 0.999 with a range of 35.0-105.0 pg/ml using linear regression model. The drug showed instability in the solution state (under acidic, alkaline and oxidative stress conditions), but it was relatively stable in the solid-state, at thermal and photo degradation conditions. |
