Bioanalytical LC-QTOF/MS Method for a N-phenylpiperazine Derivate (LQFM05): An Anxiolytic- and Antidepressant-like Prototype Drug Applied to Pharmacokinetic and Biodistribution Studies

The LQFM05 is a prototype drug designed for treatment of psychiatric disorders, such as schizophrenia, exhibiting anxiolytic- and antidepressant-like (12 or 24 µmol/kg) effects in classical behavioral tests. In order to evaluate its pharmacokinetic properties, liquid chromatography method coupled quadrupole time flight mass spectrometry system (LC-QTOF/MS) was developed fully validated analysis rat plasma tissue samples (brain, heart, liver, kidneys). Liquid–liquid extraction, solid phase extraction protein precipitation were assessed clean-up procedures biological analyte enrichment. Plasma underwent preliminary step, using acetonitrile. Linearity demonstrated the dynamic range (10.0 900.0 ng/mL), with r2 values higher than 0.99 (RSDslope ≤ 2%, Fcal < Ftab, Ccal Ctab). Biodistribution studies rats revealed high brain concentrations (12.4 µg/g), suggesting elevated affinity main therapeutic target tissue, showing blood partition coefficient 1.9. Kidneys also showed great exposure affinity, potential extrahepatic clearance. Likewise, all examined tissues exhibited satisfactory LQFMF05 distribution. fragmentation spectrum indicated presence metabolite, LQFM235, yielded by hepatic hydroxylation route, an equally bioactive derivative. Lastly, LC-QTOF/MS shown be sensitive (LOQ = 10 precise accurate determination homogenates samples.