Pharmacokinetics Of Ezetimibe Tablets And Sarpogrelate Hydrochloride Tablets In Healthy Chinese Volunteers

Section one:Pharmacokinetics of ezetimibe tablets in healthy Chinese volunteersObjective:A method for the determination of ezetimibe in human plasma was established by LC-MS/MS,and the validated method was used to study the pharmacokinetics of ezetimibe in healthy Chinese subjectsMethod:With indapamide as the internal standard,acetonitrile as the organic phase,pure water as the water phase,Hedera ODS-2 column(2.1×150 mm,5 μm,Hanbon Sci&Tech,China)as the chromatographic column,the plasma samples of ezetimibe were separated by gradient elution procedure.The MS detection was performed with multiple reaction monitoring(MRM)in negative ion mode,and the ion pairm/z 408.5→271.3(ezetimibe)and m/z 364.0→188.9(indapamide)were selected for quantitative analysis.Liquid-liquid extraction method was used for sample pretreatment,and methyl tert-butyl ether was used as extractant.Results:The method was validated in the concentration range of 0.1001 ng·mL-1～12.01 ng-mL-1,and there was no interference of matrix effect and residue.The intra-batch and inter-batch precision of ezetimibe and internal standard met the verification requirements of methodology.The method can be applied for the analysis of plasma samples of ezetimibe.The plasma concentration of ezetimibe was determined in 12 subjects after single oral administration of ezetimibe tablets.The pharmacokinetic parameters were obtained as following:8.227±5.531 ng·mL-1 for Cmax;2.79±3.30 h for Tmax;15.69±9.97 h for t1/2;135.5±87.0 ng·h·mL-1and 140.9±87.4 ng·h·mL-1for AUC0-96n and AUC0-∞,respectively.Conclusion:The established method for quantitative determination of ezetimibe in human plasma was sensitive and reliable,and has been successfully applied to the pharmacokinetic study of ezetimibe in 12 healthy Chinese subjects after a single oral administration of ezetimibe tablets.Section two:Pharmacokinetics of sarpogrelate tablets in healthy Chinese volunteersObjective:The LC-MS/MS technique was used to establish a method for the quantification of sarpogrelate in human plasma,and the validated method was used to study the pharmacokinetics of sarpogrelate in healthy Chinese subjects after oral administration.Method:With letrozole as the internal standard,Hedera ODS-2 column(2.l× 150 mm,5μm,Hanbon Sci&Tech,China)as the chromatographic column,acetonitrile:ammonium acetate aqueous solution(60:40,v/v)as the mobile phase,the plasma samples of sarpogrelate was extracted using one-step protein.The MS detection was performed with MRM in positive ion mode,and the ion pair m/z 430.2-135.4(sarpogrelate)and m/z 286.2-217.1(letrozole)were selected for quantitative analysis.Results:The method had good linear relationship in the range of 1.454 ng·mL-1-1551 ng·mL-1.The residue effect,precision,accuracy,extraction recovery rate,matrix effect and stability met the verification requirements of methodology.The method was applied to the determination of plasma samples of 22 healthy Chinese subjects after oral administration of sarpogrelate tablets,and the pharmacokinetic parameters were obtained as following:1017±481 ng·mL-1for Cmax;0.54±0.29 h for Tmax;0.76±0.17 h for t1/2;828.6±323.2 ng·h·mL-1and 833.8±327.8 ng·h·mL-1 for AUC0-5 and AUC0-∞,respectively.Conclusion:In this study,LC-MS/MS method was established to determine the plasma concentration of sarpogrelate in human plasma.This method had the advantages of high accuracy,high sensitivity and simple pretreatment,and had been successfully applied to the pharmacokinetic study of sarpogrelate tablets in 22 healthy Chinese subjects.