Studies On Pharmacokinetics And Residues Of Berberine Hydrochloride In Tilipia (Oreochromis Niloticus)

We refered the HPLC-MS/MS method for determination of berberine hydrochloridein San-Huang tablets and established the HPLC-MS/MS to detect berberine hydrochlorideresidues in tilapia(Oreochromis niloticus).And this method was used to research onpharmacokinetics after single oral administration (PO) and single intraperitoneal injection(IP) in tilapia and drug resides elimination of berberine hydrochloride after multi-dosingoral administration in tilapia at water temperature of26±2℃,respectively.The results asfollows:1.The berberine hydrochloride residues were extracted from tissues by1%formic acidmethanol. After homogeneity and centrifuge, the extract was evaporated by nitrogen andresidue was dissolved by5mLmethanol.Then the dissolved liquid was filtered with0.22μmmembrane followed by HPLC-MS-MS. The results showed that the standard curves werelinear for two analyzes at0.0～100.0ng/mL of berberine hydrochloride. Under differentlevels of tilapia blank group add recovery test, the average recoveries of berberinehydrochloride and the relative standard deviation were between91.12~102.88%and1.32~2.98%,respectively. The limit of detection was1ng/mL.All conditions can fulfill drugresidue detection needs.2.Pharmacokinetics and tissue distributions of berberine hydrochloride were studiedafter oral administration at a single dose of30mg/kg body weight and intraperitonealinjection at a single dose of10mg/kg body weight in tilapia at water temperature of26±2℃, respectively.The concentration of each tissue from low to high followed byplasma,muscle, kidney and liver after oral administration. And the concentration of each tissuefrom low to high followed by plasma, muscle, liver, kidney after intraperitoneal injection.Oral administration’s plasma drug concentration were lower than intraperitoneal injection’s.Pharmacokinetic characteristics of berberine hydrochloride in tilapia manifested that rapidabsorption, wide distribution, and long elimination half-life. Berberine hydrochloride was absorbed and eliminated slower, but distributed more widely after oral administration thanintraperitoneal injection.The plasma concentration-time conformed to two-compartmentopen models at both delivery ways.Pharmacokinetic parameters as follows：The absorptionhalf-life (t1/2ka) of berberine hydrochloride were found to be0.18h after PO and0.004hafter IP, whereas the elimination half-life (t1/2β) of berberine hydrochloride were63.838hafter PO and40.027h after IP.The distribution of apparent volume (Vd) of berberinehydrochloride were estimated to be805.837L/kg after PO and83.379L/kg after IP. Themaximum plasma concentration (Cmax) with2.95ng/mL and104.49ng/mL were obtainedat1h after PO and0.5h after IP, respectively.The areas under the curve (AUC) were115.182ng/l.h after PO and924.218ng/l.h after IP.3.The dose of30mg/kg body weight of berberine hydrochloride were oraladministration for three consecutive days in tilapia at water temperature of26±2℃.Theresidue elimination were studied in the tissue and results showed that the drugconcentration in four kinds of organization overall from low to high followed by plasma,muscle, kidney and liver.Drug concentration decreased gradually with time. Drugelimination half-life (t1/2β) in plasma, muscle, liver and kidney of tilapiawere2.33,7.62,1.30and1.62days, respectively,showing that the elimination was veryslowly.Under this breeding environment in this test, in order to ensure food safety wesuggest that the maximum residue limitation was10μg/kg and the withdrawal was morethan7days.