Pharmacokinetic Study Of Lupeol In Rat Plasma

Lupeol,a pentacyclic lupane-type triterpene represented in plant,fungi and animal kingdoms,has been paid considerable attention because of its various biological activities like anticancer,anti-inflammatory,anti-microbial,anti-mutagenic and anti-malarial activity.To elucidate the in vitro anti-cancer activity of lupeol,the cytotoxicity of lupeol activity was tested against five cancer cell lines,including AGS(human gastric adenocarcinoma cell line),DU 145(human prostate carcinoma cell line),HT29(human colon cancer cell line),2774(human ovarian cancer cell line),and NCI-H520(human lung cancer cell line),with betulinic acid as the positive control.The results indicated that lupeol has better anticancer activities against AGS and 2774 cancer cell lines than that betulinic acid did,and showed cytotoxicity against the other three tested cancer cell lines as well.Lupeol are not easily ionized by electrospray ionization.Therefore precolumn derivatization was used and p-toluenesulfony isocyanate(PTSI)was chosen as the derivatization reagent.An LC-ESI/MS/MS method was developed and validated for the quantification of lupeol in rat plasma.Samples were separated on an ACQ UPLC BEH phenyl column which was equilibrated and gradient eluted with acetonitrile and water(5 mmol/L ammonium acetate)at a flow rate of 0.25 mL/min.The detection was performed in negative ion mode by multiple reaction monitoring(MRM).The precursor/product transition(m/z)was 622.5→423.2 for quantification.The method was selective,sensitive and linear.The precision,accuracy,stability and recovery were also within an acceptable range.The pharmacokinetic study of lupeol in rat plasma was investigated after i.g.administration at a dose of 250 mg/kg.According to the mean concentration-time curve and pharmacokinetic parameters,the level of lupeol reached the maximum concentration at about 6 h after i.g.administration,and declined slowly,almost cleared all at 48 h.