Objective To establish a novel method for determination of MELE concentration in plasma and to study its pharmacokinetics
and
bioavailability in rats.Methods MELE dissolved in normal saline was administered in a dose of 5 mg/kg via gastric infusion and by intravenous injection in rats.Plasma was colleted from the jugular artery cannula and concentration of MELE was determined using a reversed phase HPLC assay with
fluorescence detection.The data was processed with the software 3P87.The pharmaceutical parameters of MELE were calculated and its absolute bioavailability was evaluated.(Results)A good linearity was obtained from 0.02 μg/ml to 3.00 μg/ml of MELE with a correlation coefficient of 0.9999.The detection limit was 0.02 μg/ml.The extraction recovery was more than 80 %.The RSD for the intra-day and inter-day was less than 10%.The concentration time profile after intravenous administration was found to be fitted to an open two-compartment model.The half-lives for the distribution phase and elimination phase were(4.22±5.58) min and(58.53±17.60) min respectively.The total area under the plasma concentration-time curve(AUC),the volume of the central compartment and plasma clearance were(133.40±9.27)(μg·min)/ml,(0.27±0.15) L/kg and(7.50±0.53) ml/(g·min),respectively.The concentration time curve after gastric infusion was fitted to an open one-compartment model.The peak time,peak concentration and AUC were(14.29±3.28) min,(0.64±0.11) μg/ml and(54.35±9.34)(μg·min)/ml,respectively.Conclusion HPLC assay with fluorescence detection was sensitive,specific,rapid and reproducible,and could be used for quantitative analysis of MELE in vivo.The absolute bioavailability of MELE in rats was 40.74 %.