Development of a New, Fully Validated LC-MS/MS Method for the Analysis of Flibanserin in Pharmaceutical Preparations and Comparison of the Chromatographic Performance with Six Stationary Phase Types

Abstract

Background: Initially synthesized as an antidepressant and potentially rapid onset of action, flibanserin (FLB) was approved by the Food and Drug Administration (FDA) in August 2015 with a warning to dispense the drug through a dedicated risk management program, despite the removal of HSDD from the DSM-5TM. The drug is the first noteworthy FDA-approved drug for treating premenopausal women with acquired, generalized HSDD. Objective: In literature, studies are plasma analyses or metabolite determinations to meet pharmacokinetic analyses and some analytical targets. For this reason, in this thesis, a new method has been developed for analysing FLB from pharmaceutical preparations, which is our target, providing all optimization conditions and method validity parameters. Methods: The chromatographic separation was also investigated using Chromolith® and Ascentis® Express models with a total of six stationary phases. The mobile phase mixture was acetonitrile:ammonium formate (0.020 M, pH 6.0) and was used at the ratio (60:40, v/v). The optimum column temperature was chosen as 40.0±0.1°C, and the autosampler thermostat temperature was chosen as 15±0.1°C. The sample injection volume is optimized to be 1 μL. Results: The developed method is linear in the range of 2.63–105.0 ng/mL, and the regression coefficient is 0.999 intraday and 0.986 interday. In the method, LOD and LOQ were obtained as 128 pg/mL and 384 pg/mL, respectively. In addition, the ANOVA P values were calculated as 0.586 and 0.914, respectively, in the validation studies conducted intraday and interday. Conclusion: FLB chromatographic behaviors were studied and compared in detail with six different stationary phases. The developed method was fully validated according to the ICH Q2 (R1) guideline, and its pseudo-pharmaceutical formulation was analyzed.