Pharmacokinetic Studies Of Diterpenoids From Andrographis Paniculata

Objective To develop and validate specific,rapid,and sensitive methods for quantitative analysis of andrographolide,dehydro andrographolide, neoandrographolide simutineously in plasma by liquid chromatographic-tandem mass spectrometry and be applided to study their pharmacokinetics.The pharmacokinetic features were interpreted for chuanxinlian tablet,the diterpenoids from Andrographis paniculata(andrographolide,dehydroandrographolide and neoandrographolide) and the monomer mixtures including andrographolide, dehydroandrographolide,neoandrographolide respectively.To elucidate the difference of the pharmacokinetic behavior and the interactions among andrographolide,dehydroandrographolide,neoandrographolide.Methods This study were composed of five animal testing sections and there were 6 rats for each section.The rats were lavaged with chuanxinlian tablet, andrographolide,dehydroandrographolide,neoandrographolide and the monomer mixtures.Blood samples were collected before and 5 min,15 min,30 min,50 min, 70 min,90 min,2h,4h,8h and 12h from rat after dosage.Plasma was separated by centrifugation of the heparinized samples at 3000 rpm for 10 min and was stored at -20℃until analysis.After a simple protein precipitation using methanol,the samples were detected by LC/MS/MS.The concentration-time data was analyzed by non-compartmental methods in order to obtain the pharmacokinetic parameters.Results The study indicated that the andrographolide,dehydroandrographolide and neoandrographolide in chuanxinlian tablet could be absorded into rat blood.The main pharmacokineitic parameters of andrographolide,dehydroandrographolide and neoandrographolide were as followed:C_max=1.441μg/mL,T_max=1.6h,K_e=0.1 h^-1; C_max=5.459μg/mL,T_max=0.6h,K_e=0.1h^-1;C_max=2.32μg/mL,T_max=0.89h,K_e=0.79 h^-1.These data showed that they were absorded into blood rapidly and eliminated slowly.The andrographolide and neoandrographolide couldn't be found in rat blood when rat was lavaged with the monomer of andrographolide or neoandrographolide. The monomer of dehydroandrographolide could be absorded into rat blood.But compared to the dehydroandrograholide in chuanxinlian tablet,the monomer of dehydroandrographolide in rat was more slowly absorded(T_max=1.6h),more quickly eliminated(K_e=0.56h^-1) and the bioavailability was more worse.After the rats taken the mix of andrographolide,dehydroandrograholide and neoandrograholide,the blood drug level didn't change almostly from 5 min to 12 h.Conclusions The fully validated LC/MS/MS method has been successfully applied to the pharmacokinetic studies of andrographolide,dehydroandrographolide, neoandrographolide in rat plasma;The pharmacokinetic features of diterpenoids from Andrographis paniculata were significantly different and couldn't replace each other.