OBJECTIVE:To establish an HPLC method for the determination of dextromethorphan and dextrophan in human urine and to discriminate phenotype of CYP2D6.METHODS:The urine samples were hydrolyzed by enzyme,distilled and purified by acid and alkali before direct introduction.HPLC system was adopted using Waters Nova-Pak Phenyl column with mobile phase consisted of acetonitrile-water(60∶40)at a flow rate of 1.0 mL?min-1.The fluorescence detection was performed with excitation wavelength at 280 nm and emission wavelength at 310 nm.The column temperature was 25℃.RESULTS:The linear ranges of dextromethorphan and dextrophan were 0.065～4.148 ?g?mL-1(r=0.998 5)and 0.353～22.592 ?g?mL-1(r=0.999 7),respectively.The lower detection limits were 0.016 ?g?mL-1 and 0.018 ?g?mL-1,respectively.The average recoveries were 90.5% and 93.5%,resepctively;the intra-day RSD were no more than 3.26% and 3.47% and inter-day RSD were no more than 3.65% and 4.05%,respectively.All the 8 subjects were extensive metabolizers(EM).CONCLUSION:The method is simple and reliable,and suitable for the determination of both dextromethorphan and dextrophan in human urine and as well as the study of the phenotype of CYP2D6 polymorphisms.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.