A Different Perspective on the Characterization of a New Degradation Product of Flibanserin With HPLC-DAD-ESI-IT-TOF-MSn and Its Pharmaceutical Formulation Analysis With Inter-Laboratory Comparison

Geven A., ÖZCAN S., LEVENT S., CAN N. Ö.

JOURNAL OF AOAC INTERNATIONAL, no.5, pp.1145-1153, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1093/jaoacint/qsad074
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, DIALNET
  • Page Numbers: pp.1145-1153
  • Anadolu University Affiliated: Yes


Background Flibanserin (FLB) was first synthesized as an antidepressant drug; however, due to its enhancing effects on sexual activity, it was approved for treatment of hypoactive sexual desire disorder in women in 2015. Objective The aim of this study was to develop a new and fully validated HPLC method for analysis of FLB in pharmaceutical formulations besides its degradation products, and identification of possible formation mechanisms by using HPLC-DAD-ESI-IT-TOF-MSn. Method The HPLC separation was achieved in a Supelco Ascentis(& REG;) Express series phenyl hexyl column (100 x 4.6 mm, ID 2.7 & mu;m). The mobile phase was acetonitrile-ammonium acetate solution (50:50, v/v, 10 mM, pH 5.4) mixture, which was pumped at the rate of 0.5 mL/min. Chromatography, detection, and structural identification was performed by using a LCMS-IT-TOF instrument (Shimadzu, Japan). Results 1-(2-(4-(3-hydroxy-5-(trifluoromethyl)phenyl)piperazine-1-yl)ethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one is proposed as a novel degradation product, with a mass of 407.1695 and a formula of C20H21F3N4O2 with a margin of error about 0.001 ppm. The developed method is applicable with 98% accuracy within the 2.5-50.0 & mu;g/mL range. The LOD and LOQ were about 500 ng/mL and 1.50 & mu;g/mL, respectively. The transferability and variation between laboratories were tested by inter-laboratory comparison and evaluated with one-way analysis of variance. Conclusions A novel FLB degradation product, which was produced under oxidative forced degradation conditions was observed and identified for the first time; in addition, the formation kinetics of the degradation product besides decomposition of FLB was studied. Furthermore, an inter-laboratory comparison was carried out, and application of the proposed method on a pseudo Addyi(& REG;) (Sprout Pharmaceuticals, Inc.) sample was tested using both instrument configurations.