Development of a new strategy for the analysis of chemical medications in serum with HPLC using protein precipitation,on-line SPE and column switching
作者单位：Laboratory of Clinical PsychopharmacologyBeijing Key Lab of Mental DisordersBeijing Anding HospitalCapital Medical University
会议名称：《中国药理学会第三届全国治疗药物监测学术年会》
会议日期：2013年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：finacial suports from the National Science and Technology Major Project for Investigational New Drug(2012ZX09303-003) Capital Medical Research Development Fund of China(2007-3087,2009-3135) the Science and Technology Innovation Platform Construction Project of Beijing Education Commission (PXM2011_014226_07_000089)
关 键 词：Protein Precipitation On-line SPE Column Switching High Performance Liquid Chromatography
摘 要：Analysis of drug concentration in serum/plasma with high performance liquid chromatography (HPLC) is widely used in both overall drug development process and therapeutic drug monitoring (TDM).Commonly used HPLC is ordinarily a single channel system consists of one pump and one column with auto-sampler,detector and working *** samples must be pre treated before injection into the *** sample preparation techniques include liquid-liquid extraction(LLE),solid-phase extrction(SPE) and protein precipitation(PP).The former two techniques are always labour intensive,low detection through-put and error prone processes with multi-step manual *** is a simple and easy handling technique,but the supernatant is always impure with large volumn. Dual chanel HPLC with two pumps,two columns and one switching valve has been developed in the last decades to do on-line SPE with direct injection of serum or plasma into the *** types of on-line SPE columns are commercially available:the different kinds of reverse-phase(RP) columns,restricted access material(RAM) columns and turbulent flow chromatography(TFC) *** columns are easily to be contaminated and clogged,and need to be changed *** and TFC columns function as a pre-column,in combination with an analytical column and column switching,to remove proteinaceous materials prior to analytical chromatographic *** on-line SPE methods have been reported for the determination of different kinds of medications/metabolites in serum or *** these mehtods have not been widely used,because of short on-line SPE column life-time,low drug recovery and high costs. We have developed a new strategy by combining PP,on-line SPE and column switching together. The protein precipitation reagent we used has a very high protein removal efficiency(99.4%), high drug extraction efficiency(70%) and low organic solvent usage(less than the sample volumn).After centrifugation,the s