Insights into flibanserin oxidative stress degradation pathway: in silico – in vitro toxicity assessment of its degradates

Abstract

Characterization of the degradation products of pharmaceutical drugs is essential to assess their safety.

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

“…Moreover, it has been observed that FLB is quite stable against UV light, acidic and basic environments, and moisture and does not give any degradation products. The results obtained here are similar to the literature, because no degradation product has been found in the stability-indicating studies of FLB until today ( 11 , 21 , 22 ).…”

“…In the stability-indicating studies on FLB, the forced degradation conditions were carried out in four different ways: 3% H 2 O 2 at 100°C ( 17 ), 3% H 2 O 2 ( 11 ) and 15% H 2 O 2 in a water bath, and 3% H 2 O 2 ( 19 ) and 2.4% H 2 O 2 ( 13 ) at room temperature, previously. The degradation products obtained were broken up of FLB at high temperatures under the forced oxidative conditions.…”

“…LC-MS/MS is the dominant technique, and C 18 bonded silica-based particle columns are the most widely used stationary phases in the previously reported methods ( 6–10 ); all the columns used in these assays are relatively short, narrow, and small particle columns produced with recent technologies. Moreover, there is also a limited number of HPLC studies on FLB analysis in which detection was absorbance-based ( see Supplemental Table S1 ); no internal standard was used in these methods ( 11 , 12 ), and analyses were performed by using classical C 18 particle columns ( 11 , 13 – 15 ). On the other hand, there are some other applications in the literature, in which different analytical techniques were used: analysis of Flibanorin ® film-coated tablets and human plasma using thin-layer chromatography ( 16 ), first-derivative spectrophotometric methods for determination of FLB in Veroxeserin ® tablets in the presence of its oxidative degradation products ( 17 ), second-derivative synchronous fluorimetric method for determination of FLB and sitagliptin phosphate in synthetic mixtures and human plasma samples ( 18 ), and characterization of N -oxide metabolite by LC-MS and NMR spectroscopy ( 19 ).…”

Cardioprotective Effect of Flibanserin against Isoproterenol-Induced Myocardial Infarction in Female Rats: Role of Cardiac 5-HT2A Receptor Gene/5-HT/Ca2+ Pathway

“…Animal care and experimental procedures were approved by the Institutional Research Ethics Committee at the Faculty of Pharmacy Suez Canal University, ethical approval number 201903MA1. The median lethal dose (LD50) of ISO in rats was found to be 600 mg/kg S.C. [84], and the LD50 of FLP in rats is 3.844 g/kg orally, while and maximum tolerated dose of FLP in rats is 0.058 g/kg [85], FLP dose selection was based on previous experiments [86][87][88][89].…”

The anti-COVID-19 drug Favipiravir: Degradation, Method development, Validation, NMR/LC–MS characterization, and In-vitro safety evaluation

“…The colorimetric analysis yields a total protein mass estimate that is proportional to the number of cells present. FVP and its breakdown products (FDP 1 and FDP 2) were tested in vitro against NHSF cell lines to determine their potential toxicity and/or safety (Ahmed et al 2020 ; Mohammed F. El-Behairy et al 2021 ). The effect of these chemicals on the viability and proliferation of the NHSF cell line was assessed using the SRB assay, as well as photos taken with an optical microscope to detect any morphological changes on the examined cells.…”