Determination Of Memantine Hydrochloride And Donepezil In Human Plasma By LC-MS\MS Method

Alzheimer’s disease(ad),also known as dementia,is a degenerative neurological disease with progressive onset and hidden development.Dementia is characterized by degeneration of cognition,function,and behavior,and patients bring to society This task established a lc-ms/ms method to determine the concentration of memantine(mm)and donepezil(dpz)in human plasma,verified the methodology of the method,and combined the memantine and donepezil Study of pharmacokinetics of medication in vivo.LC/MS was used to analyze and quantify the analytes memantine hydrochloride and donepezil using the internal standard method,and MM-d ~3(Memantine-d ~3 HCl)and DPZ-d5(Donepezil-d 5 HCl)was used to quantify the analyte,and a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was established for the simultaneous determination of memantine hydrochloride and donepezil.Validated that this method can be used in clinical studies of mm and dpz.The intra-and inter-assay precision and accuracy are high,the mm deviation is 2.7-3.4%,the dpz deviation is 0.9-3.1%,and the mm matrix effect is low.The concentration was 104±4.1%,the middle concentration was 105.0±3.0%,the high concentration was 98.6±2.4%,and the dpz matrix effect was 96.6±4.6%at low concentration,98.6±1.5%at middle concentration,and 101±1.8%at high concentration.The extraction recoveries of low,medium,and high concentrations were 91.2%,92.7%,and 93.3%.The overall average recovery was 92.4%.The recoveries of low,medium,and high concentrations of dpz were96.0%and 95.1%,respectively.,99.4%.The overall average recovery is 96.8%.In the stability study,the solution and matrix can be stored stably for 25 hours at room temperature,and can be stored for a long time at-20℃ and-80℃.In this study,pharmacokinetic calculations will be performed based on the determination of the concentrations of memantine hydrochloride and DPZ in plasma after administration.Healthy test subjects will take orally 10 mg of MM-DPZ assay reagent and orally after meals.The 90%CI of the geometric mean ratios of MM-DPZCmax,AUC0-t,and AUC0-∞in the all fall between 80.00～125.00%,indicating that the test preparation and reference preparation of 10 mg MM-DPZ tablets taken orally or after meals have Bioequivalence:Healthy testers take 10 mg MM-DPZ tablets orally after fasting and orally after meals,and the test and reference preparations are safe.