毛细管电泳对萘普生对映体的分离及定量分析

以环糊精及其衍生物作为毛细管电泳手性分离的添加剂,采用正极进样,对酸性药物萘普生对映体的分离进行研究,结果表明该途径能在较短的时间内使对映体达到基线分离。还研究了缓冲体系ｐＨ值对萘普生对映体分离的影响,结果表明,ｐＨ５．５时分离效果最佳,且耗时最短。对ＣＥ定量能力（线性,精度）进行了考察,获得满意的结果,线性相关系数为０．９９８,ＲＳＤ低于４．４％。     

毛细管电泳手性分离联萘酚

以胆酸为手性表面活性剂,通过优化其浓度及缓冲溶液的ＰＨ值实现了手性物质联萘 线分离。详细研究了乙腈对分离的影响,并考察了甲醇,２－丙醇脏 甲基甲酰胺（ＤＭＦ）等有机试剂的影响。     

Derivatized cyclodextrins for the separation of enantiomers in capillary electrophoresis

The use of cyclodextrin derivatives for the efficient separation of enantiomeric drugs is described. Hydroxypropylation, methylation or carboxymethylation of the cyclodextrin not only result in a better solubility of the cyclodextrin in aqueous solutions, but also favor, via additional hydrogen bonding, the stabilization of one of the cyclodextrin-analyte complexes. The influence of the background electrolyte on peak shape is also described here. Carboxymethylated cyclodextrin can be used in similar manner to uncharged cyclodextrins at low pH values (below 4). At pH values above 5, however, its charge also allows the separation of uncharged enantiomers as in a micellar-like system.     

家兔血液中西咪替丁的微透析-毛细管电泳测定研究

本文报道用微透析毛细管电泳测定家兔血液中的西咪替丁。研究发现,采用如下条件:100mmol/LpH2.5的磷酸盐缓冲液,分离电压17kV,电动进样9kV×9s,西咪替丁与雷尼替丁能达到基线分离,据此以雷尼替丁为内标建立了一种测定西咪替丁的方法。西咪替丁与雷尼替丁峰面积比与相应的西咪替丁浓度在8.0×10-9～4.0×10-7g/mL范围内呈线性关系(r=0.998),检出限为5.0×10-9g/mL。药物代谢动力学参数由“NDST21”计算软件求得,代谢符合一室开放模型。     

Cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography for the analysis of methadone and its metabolites in serum of heroin addicts

Methadone (MET) metabolism has been largely demonstrated with a high inter-individual variability and, therefore, quantification of MET is very important for therapeutic drug monitoring. A cation-selective exhaustive injection and sweeping MEKC (CSEI-Sweeping) was first developed to analyze MET and its two metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP), in human serum. After pretreatment, the samples were electrokinetically injected into capillary (10 kV, 500s) and swept by the separation phosphate buffer (100 mM, pH 4.0) containing 20% tetrahydrofuran and 100 mM SDS at -15 kV. The LODs were 200 pg/mL for MET and EMDP, and 400 pg/mL for EDDP. Ten volunteers were administered MET (5.0-120.0 mg/day) orally for 84 days and serum samples were taken after the daily dose of MET (days 1, 2, 7, 14, 28, 56 and 84) individually. This method was used for monitoring MET and its metabolites in heroin addicts and for pharmacokinetic investigations.     

16通道毛细管阵列电泳对手性氨基酸分离条件的快速筛选

利用自行研制的16通道旋转激光扫描共焦荧光检测式毛细管阵列电泳仪,我们采用了不同浓度的十二烷基硫酸钠、β-环糊精、γ-环糊精对荧光素标记丙氨酸、甲硫氨酸、色氨酸和谷氨酸4种手性氨基酸进行了手性拆分条件研究,快速地获得了这4种手性氨基酸对映体最佳的拆分条件:分离缓冲液为10 mmol/L硼酸缓冲液(pH=10),5 mmol/Lγ-环糊精为添加剂时,4种手性氨基酸全部达到了基线分离。     

母乳中甲硝唑药物代谢动力学的毛细管电泳研究

用毛细管电泳测定了甲硝唑在母乳中的含量,研究了其药代动力学。以液－液萃取作为样品预处理手段,萃取回收率在９０％～１０１％范围内。以替硝唑作为内标,采用场放大进样。该法在甲硝唑质量浓度为０．４０～２５．６７ｍｇ／Ｌ时,甲硝唑质量浓度和甲硝唑与替硝唑的峰面积之比呈线性,线性相关系数（ｒ）大于０．９９９,最低检测量为０．４０ｍｇ／Ｌ,检出限（Ｓ／Ｎ＝３）为０．１５ｍｇ／Ｌ,相对峰面积的相对标准偏差为１．     

Study on pharmacokinetics and tissue distribution of norvancomycin in rats by CE with electrochemical detection

In this paper, we developed a sensitive and simple method to study the pharmacokinetics and tissue distribution of norvancomycin (NVCM) in experimental animals by using CE with electrochemical detection. Pharmacokinetics investigation was performed by the collection of blood samples at timed intervals following administration of NVCM. Pharmacokinetic parameters were calculated by the 3P87 pharmacokinetic program. The elimination half-life of NVCM was 42.4742 min with a clearance rate of 0.0233 mL x kg(-1) x min(-1). Additionally, drug distribution was studied by measuring the NVCM levels in kidney, lung, stomach, intestine, spleen, heart, liver, and cerebrum. Electrophoresis conditions such as buffer solution, working potential, separation voltage, and sampling time were also discussed. The linear range was from 0.8 to 540 microg/mL with a correlation coefficient of 0.9991. The detection limit was 0.3 microg/mL. This method was for the first time applied to study the pharmacokinetics and tissue distributions of NVCM in experimental animals.     

以万古霉素为手性选择剂的氨基酸对映体的毛细管电泳快速分离

建立了以万古霉素为手性分离选择剂的毛细管电泳氨基酸对映体快速分离的方法。向缓冲溶液中加入０．００２％（Ｗ／Ｖ）的（１,５－二甲基－１,５－二氮杂十一烷亚甲基聚Ｎ－甲溴化物（ｈｅｘａｄｉｍｅｔｈｒｉｎｅ ｂｒｏｍｉｄｅ ＨＤＢ）做电渗流改性剂,使电渗流的迁移方向反转,与分析物方向一致,缩短了分析时间。此外,ＨＤＢ还使毛细管壁得到动态修饰,减少了万古霉素在毛细管壁上的吸附,从而提高了柱效。考察了缓冲溶     

毛细管电泳-电化学发光法研究阿莫西林在人尿中的药代动力学

建立了毛细管电泳一电化学发光(CE-ECL)法测定人尿中阿莫西林的新方法,并将该方法用于人尿中阿莫西林药代动力学的研究.结果表明:阿莫西林在尿液中平均回收率为95.35%,该方法的线性范围为0.001～5.0μg/mL,检出限(3σ)为0.32ng/mL,对1.0μg/mL阿莫西林连续测定6次,其相对标准偏差小于2.0%.给药后6 h内的排泄率为44.54%,人尿中阿莫西林最大药物浓度出现时间为1.0～1.5 h.本方法用于人尿中阿莫西林药代动力学的研究具有快速、简便、灵敏、样品用量少等特点.     

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

The further development and application of capillary electromigration techniques for the enantioselective determination of drugs and their metabolites in body fluids, tissues, and in vitro preparations during the 2010 to 2020 time period continued to proof their usefulness and attractiveness in bioanalysis. This review discusses the principles and important aspects of capillary electrophoresis- based chiral drug bioassays, provides a survey of the assays reported during the past 10 years and presents an overview of the key achievements encountered in that time period. For systems with charged chiral selectors, special attention is paid on assays that feature field-amplified sample injection to enable the determination of ppb levels of analytes and optimized online incubation procedures for the rapid assessment of a metabolic pathway. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the impact of inhibitors on metabolic steps, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and drug enantiomers in toxicological, forensic, and doping analysis.     

Protein separation by capillary gel electrophoresis: A review

Capillary gel electrophoresis (CGE) has been used for protein separation for more than two decades. Due to the technology advancement, current CGE methods are becoming more and more robust and reliable for protein analysis, and some of the methods have been routinely used for the analysis of protein-based pharmaceuticals and quality controls. In light of this progress, we survey 147 papers related to CGE separations of proteins and present an overview of this technology. We first introduce briefly the early development of CGE. We then review the methodology, in which we specifically describe the matrices, coatings, and detection strategies used in CGE. CGE using microfabricated channels and incorporation of CGE with two-dimensional protein separations are also discussed in this section. We finally present a few representative applications of CGE for separating proteins in real-world samples.     

Analysis of enantiomers in biological matrices by charged cyclodextrin-mediated capillary zone electrophoresis in column-coupling arrangement with capillary isotachophoresis

The possibility to apply charged chiral selector as buffer additive in capillary zone electrophoresis (CZE) on-line coupled with capillary isotachophoresis (CITP) was studied. Enantioseparations and determinations of trace (ng/ml) antihistaminic drugs [pheniramine (PHM), dimethindene (DIM), dioxopromethazine (DIO)] present in samples of complex ionic matrices (urine) served as model examples. A negatively charged carboxyethyl-β-cyclodextrin (CE-β-CD) was used as a chiral selector in analytical CZE stage following upon a sample pretreatment by CITP (preconcentration of the analytes from 5 to 20-times diluted urine samples, partial sample clean up removing macroconstituents from the sample matrices). A high recognition capability of the oppositely charged CE-β-CD was demonstrated by enantioselective retardation of the drugs in presence of micro-and semi-macroconstituents migrating in CZE stage and detectable by UV detector. In this way, enantiomers of the drugs could be easily separated and determined. Due to lack of interferences between the drugs and sample-matrix constituents in presence of charged CE-β-CD, demands on both spacers in CITP step and multiple column-switching were minimized. CITP-CZE method with charged selector appeared to be a useful analytical approach for the trace enantiomers in complex ionic matrices as it combined enhanced separation selectivity and sample loadabitlity with high separation efficiency and provided favorable performance parameters including sensitivity, linearity, precision, accuracy/recovery and robustness with minimal demands on sample preparation. Analysis of urine sample taken from a patient treated by PHM, showing concentration profile of PHM enantiomers and their metabolites, illustrated potentialities of the method in clinical research.