常见毒品的毛细管电泳分析

系统地研究了毛细管电泳分析中各种因素对常见毒品混合物分析的影响，用均匀设计确定了适用几类毒品分离分析的最佳电泳条件。并采用固相提取技术、毛细管区带电泳检测方法对血和尿生物检材中的冰毒、吗啡、单乙酰吗啡、可待因、海洛因等毒品进行了测定。通过对各种提取剂回收率的测定，认为ＧＤＸ３０１和反相Ｃ１８提取效果较好；并考察了几种毒品的线性关系、最小检测量等，为体内毒品分析提供了一些可借鉴的数据     

毒品与化学*

毒品与化学的种种纠葛在2018年中国毒品形势报告中得到了淋漓尽致的体现,因此为做好禁毒工作,必须厘清化学与毒品的关系。从为什么毒品是化学品(毒品的本质),毒品检验和识别,毒品成瘾的本质,由传统毒品到新型毒品的转变等4个方面系统阐述毒品与化学的关系。     

某些滥用药物分析的进展

本文以滥用药物吗啡和可卡因的分析检测为例，对当前毒品分析的几种主要应用技术进行简要介绍。这些方法包括物理化学方法和免疫化学方法，侧重阐述滥用药物免疫分析法，强调了免疫分析技术在毒品分析中的特殊优越性。指出发展免疫分析化学研究是加强我国毒品检测能力的一条有效途径。     

表面增强拉曼光谱在毒品检测中的应用进展

表面增强拉曼光谱(surfaced-enhanced Raman spectroscopy,SERS)作为一种借助贵金属纳米材料可以增强目标分子信号的拉曼光谱技术,由于其具有指纹识别、高灵敏、高准确度、快速无损、不受水分子干扰等特点,在法庭科学领域中的痕量毒品检测方面逐渐受到人们的关注.SERS不仅用于毒品纯品的检测,对于复杂体系的缴获毒品和人体检材毒品的检测也逐渐成为研究热点.本文重点总结了SERS检测毒品的种类和方法,介绍了用于毒品检测的增强基底的发展,以及基于SERS的检测技术的进展,并对SERS毒品检测数据的分析方法做了概括.最后讨论了SERS在毒品检测面临的主要挑战,并展望了基于SERS毒品痕量检测的未来发展趋势.     

色谱-质谱联用法测定污水中毒品含量的方法比较

污水分析法因其客观、简便等优点，已被越来越多的地方政府用于区域毒情评估。此文建立了高效液相色谱-串联质谱法测定污水中13种毒品及其代谢物和人口标记物，并对离线方法和在线方法进行了比较。离线和在线方法的线性相关系数(R²)均≥0.9970,六次平行测定浓度的相对标准偏差(RSD)分别在0.2～2.5%和0.7～6.7%之间，低、中、高水平的加标回收率分别在88.3～109.8%和98.7～117.6%之间。离线方法对分析仪器的配置和灵敏度要求更低，在样品基质过于复杂、干扰峰难以分辨时更有优势，在线方法的前处理更简单，时间和人力成本更低。将以上方法应用于171个污水处理厂样品中毒品的检测，两种方法的检测结果无显著差别，均能满足污水样品中毒品检测的要求。同时，为了解决某些基质复杂的污水样品检测时存在干扰的问题，还介绍了一种针对特殊污水样品的毒品准确定量的色谱分析思路和策略，以提高方法的通用性、准确性和分析效率，为毒品滥用情况评估提供可靠、高效的分析手段。     

利用显微拉曼光谱结合化学计量学检验包装物中的毒品

利用显微拉曼光谱对包装物中的常见毒品进行了检验,分别分析了同种包装物中的五种常见毒品,以及同种毒品在物证袋、塑料袋、半透明文件夹、玻璃片、牛皮纸袋等五种不同的包装物中的拉曼光谱。并测量了硅片上的毒品样品粉末作为对照。实验结果表明,通过将激光光斑聚焦于包装物中的毒品,可以通过其特征峰对毒品的种类进行识别,但是需要排除2875.0 cm^-1处毒品和物证袋共有的特征峰的干扰。该方法可以适用于各类透明和半透明包装物,对于非透明包装物,可以采用太赫兹光谱等技术作为补充。为了使分类结果更加直观,采用主成分分析法对实验数据进行进一步分析,并且将聚类结果用热图的形式加以体现。本研究为检验包装物中的毒品提供了一种快速、有效的技术方法,在毒品的现场、原位检验中具有良好的应用前景。     

干血点技术在滥用药物分析中的应用研究进展

干血点(DBS)作为一种新型的采血技术被广泛应用于临床以及人体中重要物质的测定等领域，与此同时在毒品分析领域中的应用也不断增加。DBS技术具有需血量少、操作简单、稳定性强和易于保存运输等优点，完美契合了毒品分析中对检材处理的需求。与全血分析相比，DBS与液质联用等检测方法结合对部分常见毒品的分析结果展现出了独特的优势。本文对DBS采样技术在滥用药物分析中的应用、难点、解决措施和发展前景进行了综述，旨在为法庭科学中深入研究和开发DBS技术的应用提供参考。     

Capillary Electrophoretic Analysis of Common Illicit Drugs

系统地研究了毛细管电泳分析中各种因素对常见毒品混合物分析的影响,用均匀设计确定了适用几类毒品分离分析的最佳电泳条件。 并采用固相提取技术、毛细管区带电泳检测方法对血和尿生物检材中的冰毒、 吗啡、 单乙酰吗啡、 可待因、 海洛因等毒品进行了测定。 通过对各种提取剂回收率的测定, 认为GDX301和反相C18提取效果较好; 并考察了几种毒品的线性关系、 最小检测量等, 为体内毒品分析提供了一些可借鉴的数据。     

不同基质中常见毒品检测方法研究进展

毒品犯罪已成为世界各国重点关注的突出问题。除了常见的传统毒品外,大量新型合成毒品从境外涌入国内市场,这些毒品又添加在不同的基质类型中,更加难以检测。基于此,对近年来国内外不同基质中常见毒品的前处理方法和检测技术展开了综述,展示了前处理方法的提取效率和不同检测技术的检测效果;对于仪器检测技术而言,给出了样品的定量限和检出限、线性关系、回收率等具体数据,并对检测方法做了总结和展望,以期对科研和实际办案提供一定参考。     

毒品检测芯片1次可快速查出10类毒品

日前,公安部科技信息化局主持了对吉林省公安厅物证鉴定中心承担的“十一五”国家科技支撑计划项目“组合型常见毒品现场快速检测技术研究”的课题验收。专家一致认为,课题组在表面等离子体共振技术基础上研制开发了基于两瓣电流式光电位置测定技术的现场毒品检测系统,现场一次性高通量检测多种毒品成分的生物芯片系统,窄缝进样高灵敏微流控电泳芯片样机,为毒品检测提供了新的现场快速筛查手段,部分关键技术达到国际先进水平。近年来,新的同类毒品即设计型毒品不断出现,对毒品检测鉴定提出了更高要求。国内对毒品及代谢物的快速分析,主要是利用进口的免疫试剂盒,但该方法干扰因素多,经常出现假阳性。而使用常规仪器分析检测技术每次只能对一个样品或一种毒品成分进行检测鉴定,在遇到严打专项斗争和发生突发事件,大量样本需要测定和多种毒品成分需要定性筛查时,便显出通量小、速度慢的缺陷。根据课题成果开发的具有自主知识产权的常见毒品电化学传感器,可代替进口免疫试剂盒,为不具备大型分析仪器的基础化验室办案现场提供了简易的快速筛选分析方法。其生物芯片可一次性高通量快速检测吗啡、苯丙胺、甲基苯丙胺、氯胺酮、大麻、丁丙喏啡、可卡因、美沙酮等10类毒品成分,基本涵盖了国内...     

A fully validated high-performance liquid chromatography-tandem mass spectrometry method for the determination of ethyl glucuronide in hair for the proof of strict alcohol abstinence

Hair analysis has become a powerful tool for the detection of chronic and past drug consumption. For several years, it has been possible to determine even the intake of ethanol in hair samples by detecting the ethanol metabolites ethyl glucuronide or fatty acid ethyl esters. Recently, new requirements were published for the use of EtG as an abstinence test (c _EtG < 7 pg/mg) as well as for heavy-drinking detection (c _EtG > 30 pg/mg). In order to perform abstinence tests, a sensitive LC-MS/MS procedure has been developed and fully validated according to the guidelines of forensic toxicology. The nine-point calibration curve showed linearity over the range of concentrations from 2–1,000 pg/mg. Detection and quantification limits were 1 and 4 pg/mg respectively. The intra- and inter-day precision and accuracy were always better than 20%. The validated procedure has successfully been applied to perform abstinence tests and to analyze hair samples from persons in withdrawal treatment. Concentrations between <LOQ and 400 pg/mg were determined. In some cases, interfering peaks complicated the quantification to some extent. First results using varied chromatographic conditions showed constituting results. However, modified chromatographic conditions help substantiate critical results, especially if the determined EtG concentration is close to a cut-off value.     

Proteomic profiling of human sera for discovery of potential biomarkers to monitor abstinence from alcohol abuse

Although numerous biomarkers or biomarker candidates have been discovered to detect levels of drinking and intervals of time after last drinking episode, only a few biomarkers have been applied to monitor abstinence in a longer interval (≥6 wks) from alcohol abuse. Considering sample sources, sensitivity, and specificity, new biomarkers from blood with better accuracy are needed. To address this, serum proteomic profiles were compared between pre‐ and post‐ treatment samples from subjects seeking treatment for alcohol abuse and dependence in an intensive 6wk daily outpatient program using high‐abundance plasma protein immunodepletion and LC‐MS/MS techniques. Protein identification, quantification, candidate biomarker selection, and prioritization analyses were carried out. Among the 246 quantified serum proteins, abundance of 13 and 45 proteins in female and male subjects were significantly changed (p ≤ 0.05), respectively. Of these biomarker candidate proteins, 2 (female) and 8 (male) proteins were listed in category 1, with high area under the receiver operating characteristic curve, sensitivity, specificity, and fold change. In summary, several new biomarker candidates have been identified to monitor abstinence from alcohol abuse.     

Confirmatory analysis of ethylglucuronide in urine by liquid-chromatography/electrospray ionization/tandem mass spectrometry according to forensic guidelines

beta-D-ethylglucuronide (EtG) is a stable Phase II metabolite of ethanol which can be detected in urine samples several days after elimination of ethanol. It is a useful diagnostic parameter for monitoring abstinence of alcoholics in alcohol withdrawal treatment. For this purpose, determination in urine is mainly performed by LC-MS, LC-MS/MS, or by GC-MS. For the mass spectrometric identification and detection of controlled substances in more sensitive fields such as forensic toxicology, workplace drug testing, doping analysis, and veterinary organic residue control, official guidelines have been released requiring a chromatographic separation and a minimum of two mass spectrometric transitions of the analyte. However, for detection of EtG none of the published LC-MS/MS methods could fulfill the minimum requirements of any of these guidelines. Therefore, an existing LC-MS/MS method has been modified by monitoring further MS/MS transitions instead of only one (deprotonated molecule [M - H](-)/product ions: m/z 75, 85, 113, and 159 optional) with the aim of withstanding administrative or court scrutiny in forensic or workplace drug testing cases. Full method validation has been performed in accordance to guidelines of the German Society of Toxicology and Forensic Chemistry (GTFCh) and requirements of ISO 17025. One application field in the United States is a workplace monitoring program to detect surreptitious alcohol use among recovering health professionals, who by contract had agreed on total abstinence after drug and alcohol withdrawal therapy.     

神经肽FF的构效关系研究*

多肽在机体中具有重要的生理功能,并且它具有化学合成和修饰的便利性,因此它吸引了越来越多的化学、生物学及其交叉领域研究人员的研究兴趣。神经肽FF(NPFF)作为阿片调节肽在阿片耐受等药理学方面具有重要的调节作用,然而迄今为止仍缺乏NPFF受体高选择性的激动剂和拮抗剂,从而阻碍了NPFF药理学功能及其作用机制的研究。本文简述了NPFF的发现,并综述了近几年来在NPFF的前体、受体和生理学功能等方面所取得的最新进展,结合本实验室的工作重点介绍了NPFF构效关系方面的研究,并展望了该研究方向今后的发展趋势。     

Comparison of ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) concentrations in hair for testing abstinence

Hair analysis is a powerful tool for retrospective drug analysis. By determining the minor ethanol metabolites ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) in hair, even a previous consumption of alcohol is detectable. However, previous studies showed a lack of correlation if both parameters are determined simultaneously. A further study was conducted to confirm or refute these results. One hundred and sixty hair samples were analyzed for EtG and FAEE in the context of driving ability. In 109 cases, alcohol abstinence was clearly proven and was excluded in 15 cases. In 36 cases, ambiguous results were found. Possible reasons for the deviating results are discussed. It is recommended, that in context of driving ability diagnostics the EtG result is determinant. In critical cases FAEE concentrations can be determined for checking purposes, but a negative FAEE result cannot refute a determined EtG concentration >7 pg/mg.     

Investigations on the influence of different grinding procedures on measured ethyl glucuronide concentrations in hair determined with an optimized and validated LC-MS/MS method

Ethyl glucuronide (EtG) analysis in hair is a suitable method for the retrospective determination of previous alcohol consumption. According to the German guidelines, EtG abstinence is improbable at c _EtG > 7 pg/mg in the proximal 3 cm of scalp hair. The chromatography of the routinely used liquid chromatography-tandem mass spectrometry procedure was optimized by replacing the stationary phase. To simplify sample preparation, two different mills were tested, and an optimized grinding process was developed. The new method was successfully validated according to the guidelines of the German Society of Toxicological and Forensic Chemistry. Despite a simple extraction procedure without any cleaning steps, a very high sensitivity (limit of detection, 1.7 pg/mg; limit of quantitation, 2.3 pg/mg) could be achieved. Competitive analysis showed significantly higher EtG concentrations in pulverized versus cut hair samples. The strong impact of sample preparation on the determined EtG concentrations suggests the introduction of a standardized sample preparation method to produce comparable results.     

UHPLC‐MS/MS quantification of buprenorphine,norbuprenorphine, methadone,and glucuronide conjugates in umbilical cord plasma

Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC‐MS/MS method using solid‐phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were <15% for each validated concentration. Our data establishes a 2 week maximum freezer storage window in order to achieve the most accurate cord plasma concentrations of these analytes. Additionally, we found that the umbilical cord tissue analysis was less sensitive compared with analysis with umbilical cord blood plasma, indicating that this may be a more appropriate matrix for determination of buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.     

Validation of a HPLC/MS method for simultaneous quantification of clonidine,morphine and its metabolites in human plasma

A high‐performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous quantification of morphine, morphine's major metabolites morphine‐3‐glucuronide and morphine‐6‐glucuronide, and clonidine, to support the pharmacokinetic analysis of an ongoing double‐blinded randomized clinical trial that compares the use of morphine and clonidine in infants diagnosed with neonatal abstinence syndrome. Plasma samples were processed by solid‐phase extraction and separated on an Inertsil ODS‐3 (4 μm) column using an 0.1% formic acid in water–0.1% formic acid in methanol gradient. Detection of the analytes was conducted in the positive multiple reaction monitoring mode. The range of quantitation was 1–1000 ng/mL for morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide, and 0.25–100 ng/mL for clonidine. Intra‐day and inter‐day accuracy and precision were ≤15% for all analytes across the quantitation range. Extraction recovery rates were ≥94% for morphine, ≥90% for M3G, ≥87% for M6G and ≥ 79% for clonidine. Matrix effect ranged from 85–94% for clonidine to 101–106% for M3G. The method fulfilled all predetermined acceptance criteria and required only 100 μL of starting plasma volume. Furthermore, it was successfully applied to 30 clinical trial plasma samples.     

A high-performance liquid chromatographic-tandem mass spectrometric method for the determination of ethyl glucuronide and ethyl sulfate in urine validated according to forensic guidelines

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are powerful markers for alcohol intake and abuse. Several analytical procedures for the quantification of EtG and EtG in serum and urine have been developed so far. Many of the published methods show limits of detections (LODs) or limits of quantifications (LOQs) for EtG in urine within the range of 0.1 mg/L or higher. Since this is the actual cutoff value for proving abstinence in Germany, problems may occur if urine samples are highly diluted. In this paper, the validation of a highly sensitive, fast and simple LC-MS-MS for the determination of EtG and EtS in urine is described. The calibration curves for EtG and EtS is linear over the whole range (0.025-2.0 mg/L). Very low detection limits can be achieved (LOD: EtG 0.005 mg/L, EtS 0.005 mg/L; and LOQ: EtG 0.019 mg/L, EtS 0.015 mg/L). All data for selectivity, precision and accuracy, recovery, as well as for the processed sample and the freeze/thaw stability, comply with the guidelines of the German Society of Toxicological and Forensic Chemistry. Strong matrix-related effects can be compensated for by using an internal standard. Finally, the applicability of the procedure is proven by analysis of 87 human urine samples and by successful participation in interlaboratory comparison tests.     

Application of LC–TOF MS to analysis of hemoglobin acetaldehyde adducts in alcohol detoxification patients

Acetaldehyde adducts of hemoglobin have been regarded as potential biochemical markers of alcohol exposure. In this study a novel sensitive method using liquid chromatography coupled to time-of-flight mass spectrometry (LC–TOF MS) has been used to investigate changes in adduct levels in alcohol detoxification patients. Hemoglobin and authentic blood samples from 66 adults with an alcohol-dependence syndrome and from 12 children were analyzed for acetaldehyde modifications with and without trypsin digestion using LC–TOF MS. After in-vitro incubation of hemoglobin with increasing concentrations of acetaldehyde, followed by tryptic digestion, 21 modified peptide fragments could be identified from their accurate mass and retention time shift. Eight of these could also be detected in authentic human blood samples. Trace amounts in children’s blood were indicative of an endogenous source. Modified peptide levels in patients’ samples with and without ethanol were significantly different, as also were levels in samples from admission and from five days later. Samples obtained 5, 10, or 15 days after admission did not differ in adduct levels. The LC–TOF MS method was sensitive enough to detect acetaldehyde-modified hemoglobin peptides in blood samples from patients with an alcohol-dependence syndrome. However, elevated levels were only observed after recent ethanol consumption and decreased during five days of abstinence, suggesting that acetaldehyde-modified tryptic peptides of hemoglobin are potential biomarkers only for short-term ethanol ingestion.