Абстрактный

QBD driven stability-indicating RP-HPLC assay method for Flibanserin; development, validation, and characterization of major degradants by LC/QTOF-MS/MS

Manish Kumar Sharma

The characteristic chemical soundness of Flibanserin (FLB) was examined by utilizing Plackett Burman plan for screening of free factors. BoxBehnken plan was utilized for optimization of tall execution fluid chromatography (HPLC) steadiness demonstrating test strategy. Constrained debasement of FLB was carried out beneath hydrolysis (acidic, fundamental, and unbiased), photolysis, oxidation and warm stretch conditions. The major oxidative debasement item was separated by preparative HPLC. The corruption item was recognized as 2-H¬Benzimidazol-2-one, 1, 3-dihydro-1-[2-[4-[3(trifluoro methyl) phenyl]-1-Noxide-piperazinyl] ethyl] taking after characterization by UV, IR, HRMS and NMR procedures.The parent particle mass of the oxidative degradants was watched mass 407.1710 and major parts (389.1582, 375.1422, 255.1100, 243.1103, 228.0866, 216.1127, and 200.0680) in LC-QTOFMS when examined in positive ionization mode. Oxidation and hydrolysis were found to be the essential corruption pathways for this particle. The chromatographic partition was accomplished on Cromasil C18 column (4.6mm×250mm, 5μm) employing a versatile stage comprising of a blend of ammonium acetic acid derivation (pH 5.5) and acetonitrile in direct angle elution mode. The strategy was found to be direct within the concentration extend of LOQ (0.5 to 70 µg/mL). The strategy was approved as per ICH rule Q2 (R1). Corruption of FLB taken after firstorder energy beneath all test conditions. V-shaped pH-rate profile energy over the pH run 2–10 was watched with greatest steadiness at pH 6.8. In conclusion, a switch stage tall execution fluid chromatographic strategy has been created and approved for quantitation of FLB in nearness of their corruption items. The major corruption item has been distinguished and completely characterized that has not been detailed till date. Usually the primary time to report a steadiness showing measure strategy for FLB.