Development of the hplc and LC-MS/MS methods for the determination of flibenser from pharmaceutical preparations and characterization of the deterioration products with LCMS-it-tof

One of the major changes in the pharmaceutical industry has been experienced by noticing the financial size and health of female sexual dysfunction that appeared in the early 2000s. Flibanserin was developed as an antidepressant drug, and because of its pro-sexual side effects, the drug was retried for this indication in the early 2000s. Due to various indications and the use of patients under different conditions, the FDA has been refused for a long time and approved in 2015 by not being able to withstand the pressures of various civil society organizations. In this study, HPLC and LC-MS/MS methods were developed for the analysis of pharmaceutical formulations of flibanserin. HPLC method was optimized in the presence of degradation products, and a new degradation product of flibanserin was identified under oxidative forced degradation conditions. Qualitative analysis of the degradation product was done with LCMS-IT-TOF, and the formation mechanism was proposed. For the two methods developed, two groups, in the core-shell and monolithic silica structure, have tried a total of 6 stationary phases for chromatographic separation. The most successful separation was achieved with Supelco Ascentis® Express phenyl hexyl (100×4.6 mm, ID 2.7 µm) column. The mobile phase was a mixture of acetonitrile-water, 10 mM ammonium acetate (pH 5.4) for HPLC, and 20 mM ammonium formate (pH 6.0) for LC-MS/MS. Flow rate and injection volume are the same for both methods and were 0.5 mL/min and 1 µL, respectively. Besides, an inter-laboratory comparison study between another HPLC instrument and HPLC method was performed, and pseudo Addyi® sample applications were carried out for both methods.