Pharmacokinetic Study Of 10-methoxycamptothecin Based On LC-MS

10-methoxycamptothecin(MCPT)which was extracted froma a special Chinese tree Camptotheca acuminata,is one of the natural analogue of camptothecin(CPT).In this study,MCPT showed more potent anti-cancer activity and metabolizes to 10-hydroxycamptothecin(HCPT),an anti-cancer drug clinically used in China.An LC-MS/MS method for simultaneous determination of MCPT and its metabolite HCPT in rat plasma,heart,liver,spleen,lung,kidney and brain was established in the present study.Rats were orally adminstratered MCPT at a single dose of 50 mg/kg,the concentrations of MCPT and HCPT in rat plasma and heart,liver,spleen,lung,kidney and brain tissues were determined by LC-MS/MS.And the relevant pharmacokinetic parameters were calculated according to the non-compartmental model.After oral administration,the concentration of MCPT was 2.41 ng/mL within 5 minutes in rat plasma,then,in about 30 min the concentration reached the maximum,then descending rapidly.The concentration of HCPT reached the maximum in about 1 hour after oraladministration,which illustrated that MCPT transforms HCPT rapidly by Methylation.The oral bioavailability of MCPT in rats was 11.73%.In the six kinds of tissues,The concentration of MCPT in lung was the highest which is 600-fold higher than that in liver and 900-fold higher than that in kidney.This might imply that MCPT is the substrate of some transporters in lung and result in the accumulation of MCPT in lung.The concentration of MCPT in brain was the lowest in six tissues,suggesting that MCPT is difficult to entere the brain tissue via the blood-brain barrier.The concentration of HCPT in liver was the highest,then in kidney.