Study On The Pharmacoxinetics And Bioequivalence Of Flupentixol-melitracen Tablets In Healthy Volunteers

Flupentixol-melitracen tablet, which is also called deanxit, can play arole of antidepressant, antianxiety, sedative, anticonvulsant. It can be usedfor the treatment of neurosis, neurasthenia, and plant disorders. The patient’scontains both flupentixol and melitracen. And the concentration offlupentixol is very low. Therefore, the pharmacokinetics and bioequivalencestudies need to establish a sensitive method for simultaneous quantitation offlupentixol and melitracen in human plasma. These papers established aHPLC-MS method to simultaneous quantitation of flupentixol andmelitracen in human plasma, and evaluate the difference of pharmacokineticparameters and the relative bioavailability and bioequivalence offlupentixol-meliracen tablets in human body.A HPLC-MS method was established for the simultaneous quantitationof flupentixol and melitracen in human plasma in the section1. The columnwas C18(150mm×2.0mm,5μm), and the precolumn was Phenomenex C18(30mm×4mm,5μm). The mobile phase was20mmol/L ammonium acetate(pH was adjusted to4.0with acetic acid) and methanol:acetonitrile=36:19, using gradient elution. The flow rate was0.25mL/min. HPLC-ESI-MS wasused in the selectes positive ion monitoring mode. The calibrationcurve’linear range of flupentixol was0.013～1.100ng/mL(n=5; r=0.9998),the limit of quantitation (LOQ, S/N>10) was found to be0.013ng/mL. Theextraction recovery was104.49%. The percent of relative standard deviation(%RSD) of intra-day and inter-day were less than8%. The calibrationcurve’linear range of melitracen was0.450～50.000ng/mL (n=5; r=0.9997),the limit of quantitation (LOQ, S/N>10) was found to be0.450ng/mL. Theextraction recovery was103.23%. The percent of relative standard deviation(%RSD) of intra-day and inter-day were less than8%. This method isaccurate, sensitive, and proved to be suitable for the pharmacokinetic andbioequivalence studies of flupentixol-melitracen tablet.In the section2, the main pharmacokinetic parameters of test andreference tablets obtained from24healthy volunteers after single oraladministration were investigated, and the bioequivalence of two kinds offlupentixol-melitracen tablets was evaluated.24healthy volunteers wererandomly divided into two groups, in cross-over and two period design test.The concentration of flupenxiol and melitracen in human plasma wasdetermined by the HPLC-MS method established in section1. Based on theanalysis of the results and the main pharmacokinetic parameters, evaluatedthe bioequivalence. There was no difference of pharmacokinetic parametersbetween a generic flupentixol-melitracen tablet. The generic flupentixol-melitracen tablet test formulation and reference formulationwere bioequivalence in human body.