A VALIDATED FORCED DEGRADATION METHOD FOR CHARACTERIZATION OF ATAZANAVIR DEGRADANTS BY LC-MS/MSAbstract
The validated stability-indicating analytical method was developed for quantification of Atazanavir using Atazanavir-D9 as an internal standard by UPLC-ESI-MS/MS. The method was validated according to United States Pharmacopeia (USP) guideline with respect to the accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, and system suitability. Forced degradation study was validated according to International Conference on Harmonisation (ICH). For this, an isocratic condition of mobile phase comprising 10 mM Ammonium Acetate Buffer (pH: 4.0): Methanol: Acetonitrile, (20:40:40%, v/v/v) using the CORTECS C18, 90Å, 2.7 µm, 4.6 mm × 150mm. The total analysis time was 4.0 min, and the flow rate was set to 0.5 ml/min. The mass transitions of Atazanavir and Atazanavir-D9 obtained were m/z 705.3 × 167.9 and 714.9®167.9. The standard curve shows a correlation coefficient (r2) greater than 0.999 with a range of 150.0-450.0 pg/ml using the linear regression model. Forced degradation of the drug product was carried out as per the ICH guidelines with a view to establishing the stability-indicating property of this method and providing useful information about the degradation pathways, degradation products, and how the quality of a drug substance and drug product changes with time under the influence of various stressing conditions.
A. Kota * and M. V. K. Valli
Department of Pharmaceutical Analysis, Vinayaka Mission's College of Pharmacy, Kondappanaickenpatti, Salem, Tamil Nadu, India.
17 January 2020
21 January 2021
27 January 2021
01 February 2021