Abstract
BackgroundIn this work, we aim to develop and validate a fast, simple, and sensitive method for the quantitative determination of flibanserin and the exploration of its pharmacokinetics.MethodsUltra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was the method of choice for this investigation and carbamazepine was selected as an internal standard (IS). The plasma samples were processed by one-step protein precipitation using acetonitrile. The highly selective chromatographic separation of flibanserin and carbamazepine (IS) was realised using an Agilent RRHD Eclipse Plus C18 (2.1 × 50 mm, 1.8 µ) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. The analytes were detected using positive-ion electrospray ionization mass spectrometry via multiple reaction monitoring (MRM). The target fragment ions were m/z 391.3 → 161.3 for flibanserin and m/z 237.1 → 194 for carbamazepine (IS). The method was validated by linear calibration plots over the range of 100–120,000 ng/mL for flibanserin (R2 = 0.999) in rat plasma.ResultsThe extraction recovery of flibanserin was in the range of 91.5–95.8%. The determined inter- and intra-day precision was below 12.0%, and the accuracy was from − 6.6 to 12.0%. No obvious matrix effect and astaticism was observed for flibanserin. The target analytes were long-lasting and stable in rat plasma for 12 h at room temperature, 48 h at 4 °C, 30 days at − 20 °C, as well as after three freeze–thaw cycles (from − 20 °C to room temperature). The proposed method has been fully validated and successfully applied to the pharmacokinetic study of flibanserin.
Highlights
Hypoactive sexual desire disorder (HSDD) is defined as a disease that results in the recurrent or persistent absence or deficiency of desire for sexual activity and sexual fantasies, which results in pronounced distress or interpersonal difficulty [1]
Method development and optimization The liquid chromatography conditions were investigated with the goal of separating interfering analytes, improving the detection sensitivity and shortening the runtime
The flow rate was investigated over a range between 0.2 and 1.0 mL/min and the effect of the column temperature was studied in the range of 20 to 40 °C
Summary
Hypoactive sexual desire disorder (HSDD) is defined as a disease that results in the recurrent or persistent absence or deficiency of desire for sexual activity and sexual fantasies, which results in pronounced distress or interpersonal difficulty [1]. Many large-scale studies have determined that approximately one-third of premenopausal women in the US experience distress over their sexual. He et al BMC Chemistry (2019) 13:111 dopaminergic receptor activity or function may inhibit sexual desire and result in HSDD. It was demonstrated that flibanserin behaves as a 5-HT2A antagonist, and a 5-HT1A agonist, as well as having an affinity to 5-HT2B, 5-HT2C, and the dopamine receptors of D4 [8] Flibanserin inhibits serotonin and elevates the number of dopamine receptors This is believed to promote dopaminergic effects while inhibiting ‘anti-sexual’ serotonergic effects, which is associated with enhanced sexual desire. We aim to develop and validate a fast, simple, and sensitive method for the quantitative determination of flibanserin and the exploration of its pharmacokinetics
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