色谱联用技术在药物分析中的应用

简述色谱联用技术如色谱-质谱联用、色谱-固相微萃取联用和色谱-色谱联用等技术的基本特点以及在药物及其代谢产物研究、天然药物化学成分分析及生物大分子分析等方面的应用.     

液相色谱-质谱联用技术在体外药物代谢物筛查中的应用

高效液相色谱与质谱联用技术已是现代药物发现中药物代谢产物筛查和鉴定最强大的分析手段,可以从品种繁多的样品中得到丰富的信息。本文关注这些技术在体外代谢研究中的应用,尤其是在筛查和鉴定生物转化形成的化学稳定代谢产物或反应性代谢产物方面的应用。为满足指定检测任务需审慎考虑选择合适的检测仪器,在代谢产物筛查中飞行时间质谱和静电场轨道阱质谱检测效率明显高于其他类型质谱。     

LC-NMR联用技术在天然产物研究中的应用

本文综述了液相色谱-核磁共振联用的原理、操作技术和在天然产物结构分析中的应用;讨论了目前液相色谱-核磁共振在实际工作中存在的主要问题及其适用条件。     

核磁共振及其联用技术在天然产物定性定量分析中的应用

核磁共振及其联用技术可用于中药材的鉴别、化合物结构鉴定及中药有效成分的测定,具有快速、准确、专属性强、精密度好等特点,成为分析天然产物的一种重要手段.综述了近10来年核磁共振及其联用技术在天然产物定性、定量研究中的应用情况.     

液质联用技术在医药领域的发展与应用

本文介绍了液质联用技术的基本原理、分类及特点,主要论述了液质联用技术在天然产物化学成分分析,药物及其代谢产物研究,残留物分析,生物大分子分析和临床诊断等医药领域的广泛应用.     

液质联用技术在医药领域的发展与应用

本文介绍了液质联用技术的基本原理、分类及特点,主要论述了液质联用技术在天然产物化学成分分析,药物及其代谢产物研究,残留物分析,生物大分子分析和临床诊断等医药领域的广泛应用。     

色谱及其联用技术在海洋药用生物核苷类化合物筛选排重方面的应用

为了解决天然产物化学研究中核苷类化合物重复提取、分离、纯化和表征等问题,避免人力物力的大量消耗并提高新化合物的发现效率,因此对已知核苷类化合物的快速鉴别、排重显得尤为重要。本文以笔者所在课题组取得的研究成果为例,从高效液相色谱、高效液相色谱-质谱联用、毛细管电泳和毛细管电泳-质谱联用等4种色谱及其联用技术,对海洋生物中核苷类化合物快速鉴别、排重方法进行了系统介绍。上述方法可以实现对海洋药用生物粗提物中常见核苷类化合物的快速筛选、排重,避免对已知成分繁杂的分离纯化、结构鉴定过程,为海洋天然产物化学研究提供了一种新思路。     

电喷雾液质联用技术在头孢菌素研究方面的应用

随着液质联用仪器的逐渐普及与实验技术的不断发展,LC-ESI-MS技术已广泛应用于药物及其代谢产物和天然药物化学成分的研究中.然而LC-ESI-MS技术在作为医药的重要组成部分的头孢菌素方面的应用尚不广泛,本文将就目前的应用情况进行综述和下一步的研究方向进行展望.     

高效制备液相色谱在天然产物分离中的应用

综述高效制备液相色谱法在天然产物有效成分分离中的应用研究进展。用高效制备液相色谱法分离制备天然产物的单体,具有高效、操作方便、快速的优点,当其与高速逆流色谱、大孔吸附树脂及超临界CO2萃取联用时,分离效果更好。     

液-质联用中大气压电离接口技术及其在药物分析中的应用

目的：介绍液相色谱-质谱联用技术（LC-MS）在药物分析中的应用。方法：通过介绍液相色谱-质谱技术原理，引入大气压电离接口技术，并综述了在药物分析中的应用。结果：液相色谱-质谱技术对药物的杂质检查与降解产物、药动学、药物代谢产物的分析和鉴定、生物大分子以及药物开发得到了广泛应用。结论：大气压电离接口技术，扩大了液相色谱-质谱联用技术的应用范围，促进了药物分析学科的发展。     

Application of LC-MS for quantitative analysis and metabolite identification of therapeutic oligonucleotides

Therapeutic oligonucleotides (OGNs) have been studied extensively in the recent years as novel agents designed to selectively and specifically inhibit target gene expression in cell culture, in animal disease models and in human. This review summarizes applications of liquid chromatography coupled with mass spectrometry or tandem mass spectrometry (LC-MS or LC-MS/MS) for quantitative analysis of therapeutic OGNs and characterization of their metabolism in vitro and in vivo described in the literature over the past 10 years. Although the applications of LC-MS or LC-MS/MS to the molecular mass measurement, sequence determination, DNA adducts identification, detection of mutations and characterization of covalent and/or noncovalent DNA/RNA complexes have been comprehensively reviewed in a few excellent review papers. The quantitative bioanalysis and metabolite identification of therapeutic OGNs using LC-MS or LC-MS/MS have not been covered. This review covers technical issues, current approaches and applications of LC-MS or LC-MS/MS for quantitative analysis of OGNs in biological matrices and characterization of their in vitro and in vivo metabolism. Finally, some conclusions are drawn and prospects of LC-MS in quantitative analysis and metabolism characterization of therapeutic OGNs are discussed.     

液相色谱——质谱联用技术及其在天然药物分析中的应用

目的　介绍近年来液相色谱—质谱联用技术的研究进展及其在天然药物分析中的应用。方法　主要介绍液相色谱—质谱(LC -MS)接口技术中API技术的研究进展及液相色谱 -电喷雾离子化质谱(LC -ESI -MS)。液相色谱 -大气压化学离子化质谱(LC -APCI -MS)等技术在天然药物分析中的应用。结果及结论　液相色谱 -质谱在接口技术方面取得了很大进展,且随着该技术的不断完善液质联用技术在天然药物分析中占据越来越重要的地位     

液质联用技术在药物体内代谢研究中的应用

目的:探讨液质联用(LC-MS)接口技术研究及其在药物代谢中的应用。方法:查阅文献、综述液质联用接口技术研究及其在药物代谢中的应用。结果:随着各种新型接口技术,特别是电喷雾电离和大气压化学电离的引入,LC-MS技术对高极性化合物的分析具独特优势,在药物体内代谢研究中发挥着日趋重要的作用。结论:LC-MS技术在中药、抗菌药物等多种药物及其代谢物的分析检测中广泛的发挥着重要作用。     

LC-MS/MS技术及其在天然产物分析中的应用

目的:研究LC-MS/MS技术及其在天然产物分析中的应用;方法:通过分析Lc-MS接口的基本原理详细研究LC-MS/MS技术,并分别介绍其在天然产物分析中微量天然物质分析、天然产物异构体的分离和鉴定、天然产物筛选和中药指纹图谱四个方面的应用.结果和结论:LC-MS/MS在技术及应用方面取得了很大进展,相信在天然产物分析中必将发挥越来越重要的作用.     

LC-MS of palytoxin and its analogues: State of the art and future perspectives

The state of the art of LC-MS of palytoxin and its analogues is reported in the present review. MS data for palytoxin, 42-hydroxy-palytoxin, ostreocin-D, mascarenotoxins, and ovatoxins, obtained using different ionization techniques, namely fast-atom bombardment (FAB), matrix assisted laser desorption ionization (MALDI), and electrospray ionization (ESI), are summarized together with the LC-MS methods used for their detection. Application of the developed LC-MS methods to both plankton and seafood analysis is also reported, paying attention to the extraction procedures used and to limits of detection (LOD) and quantitation (LOQ) achieved. In a research setting, LC-MS has shown a good potential in determination of palytoxin and its analogues from various sources, but, in a regulatory setting, routine LC-MS analysis of palytoxins is still at a preliminary stage. The LOQ currently achieved in seafood analysis appears insufficient to detect palytoxins in shellfish extract at levels close to the tolerance limit for palytoxins (30 μg/kg) proposed by the European Food Safety Authority (EFSA, 2009). In addition, lacking of certified reference standard of palytoxins as well as of validation studies for the proposed LC-MS methods represent important issues that should be faced for future perspectives of LC-MS technique.     

液质联用技术检测硫酸多黏菌素B中各组分

目的建立硫酸多黏菌素B的液质联用分析方法,确定多黏菌素B中各组分。方法按照第6版《欧洲药典》液相色谱法分离多黏菌素B各组分,采用液质联用技术测定各个组分相对分子质量进行验证。结果多黏菌素B实际样品中存在4个组分,分别为多黏菌素B1,B2,B3,B1-I。其主要组分为多黏菌素B1。结论液质联用技术用于多粘菌素的质量控制,方法准确、可行。     

Bioanalytical LC-MS of therapeutic oligonucleotides

Therapeutic oligonucleotides (OGNTs) are important biopharmaceutical drugs for the future, due to their ability to selectively reduce or knockout the expression of target genes. For the development of OGNTs, reliable and relatively high-throughput bioanalytical methods are required to perform the quantitative bioanalysis of OGNTs and their metabolites in biological fluids (e.g., plasma, urine and tissue). Although immunoaffinity methods, especially ELISA, are currently widely applied for this purpose, the potential of LC-MS in OGNT analysis is under investigation. Owing to its inherent ability to monitor the individual target OGNTs as well as their metabolites, LC-MS is now evolving into the method-of-choice for the bioanalysis of OGNTs. In this paper, the state-of-the-art of bioanalytical LC-MS of OGNTs and their metabolites in biological fluids is critically reviewed and its advantages and limitations highlighted. Finally, the future perspective of bioanalytical LC-MS, that is, lower detection levels and potential generic LC-MS methodology, is discussed.     

Comparison of ELISA and LC-MS analyses for yessotoxins in blue mussels (Mytilus edulis).

Blue mussels (Mytilus edulis) collected from Fl?devigen Bay, Norway, in 2001 and 2002 were analysed for yessotoxins (YTXs) by ELISA and yessotoxin (YTX), 45-hydroxyYTX, and carboxyYTX by LC-MS. Results from the two methods were compared to evaluate the ELISA. The response in the ELISA was 3-13 times higher than LC-MS, probably due to the antibodies binding to other YTX analogues not included in the LC-MS analysis. Nevertheless, the correlation between ELISA and LC-MS was good, with r2 values> or =0.8. The results indicate that the ELISA is a reliable method for estimating the total level of YTXs in mussels, and are consistent with extensive metabolism of algal YTXs in mussels. YTX was a minor component in the blue mussels at all times compared to 45-hydroxyYTX and especially carboxyYTX, except when the P. reticulatum bloom occurred. The results also indicate the presence of significant amounts of YTX analogues in addition to those measured by LC-MS. All samples below 4 mg/kg by ELISA were below the current EU regulatory limit of 1 mg/kg by LC-MS. Therefore, we propose using ELISA as a screening tool with a cut-off limit at 4 mg/kg for negative samples, whereas samples above this limit would be reanalyzed by LC-MS.     

LC-MS/MS法测定人血浆中石杉碱甲浓度的不确定度分析

目的:探讨高效液相色谱串联质谱电喷雾(LC-MS/MS)法测定人血浆中石杉碱甲浓度的不确定度评定方法。方法:用LC-MS/MS法测定人血浆中石杉碱甲浓度,通过对测试方法流程进行分析,确定不确定度来源,计算合成不确定度和扩展不确定度。结果:血浆中石杉碱甲浓度测定的扩展不确定度为9.16%。结论:本评定方法适用于LC-MS/MS法测定人血浆中药物浓度的不确定度评定测量,不确定度的评定方法确立对于血药浓度的测定具有重要意义。     

Comparative LC-MS and HPLC analyses of selected antiepileptics and beta-blocking drugs

A highly sensitive and specific assay procedure based on the combination of liquid chromatography and mass spectrometry (LC-MS) has been developed for the quantitative analysis of selected antiepileptics (carbamazepine and phenytoin) and beta-blocking drugs (acebutolol, atenolol, pindolol and propranolol) using APCI as an ionization process. The measured concentration range was 100-300 ng ml-1 for all drugs except phenytoin (0.5-1.5 micrograms ml-1). Analysis was based on direct injection of methanolic solutions of drugs into the mass spectrometer with the subsequent elution with a mobile phase consisting of methanol and 1% acetic acid solution (4:1) at a flow rate 1 ml min-1. The mass spectrometer was programmed to permit detection and determination of either fragment or molecular ions of carbamazepine, phenytoin, acebutolol, atenolol, pindolol and propranolol at m/e 194.3, 252.9, 337.2, 267.1, 249.1 and 260.1, respectively. The recorded chromatograms exhibited well-resolved peaks at retention times < 1 min. The peak area was correlated linearly to the drug concentration. Intraday precision gave relative standard deviations in the range 1.75-4.02%. Compared to HPLC, the described LC-MS was faster, more sensitive and specific. Unlike HPLC, LC-MS could be applied to analyze incompletely resolved mixtures. The absolute detection limits for LC-MS and HPLC were 0.2-0.5 and 10-25 ng, respectively. Recovery studies of the investigated compounds in pharmaceutical products using LC-MS and HPLC gave mean percentages of 97.5-102.0 and 98.4-103.3, respectively. Statistical analysis of the data using t- and F-tests showed insignificant differences between both methods for the analysis of carbamazepine, phenytoin, acebutolol and atenolol in pharmaceutical formulations. However, LC-MS gave more accurate results than HPLC for determination of pindolol in tablets. Propranolol could only be determined in tablets using LC-MS.