吲唑酰胺类合成大麻素的EI质谱特征分析

采用气相色谱－质谱联用技术（GC－MS）对 9 种吲唑酰胺类合成大麻素（MDMB－CHMINACA、5F－AB－PINACA、5F－AMB、AB－CHMINACA、AB－FUBINACA、AB－PINACA、MDMB－FUBINACA、AMB－FUBINACA、ADB－BUTINACA）在电子轰击（EI）电离模式下产生的主要碎片离子和碎裂过程进行分析,并对所获得的质谱图进行解析,推测该类物质的EI碎裂规律。结果表明,在EI模式下,吲唑酰胺类合成大麻素的吲唑3号位酰胺基C—N键的断裂是主要碎裂方式,在碎裂过程中还存在麦氏重排。该研究总结了吲唑酰胺类合成大麻素在EI模式下的主要碎片离子和质谱特征,归纳了EI的特征碎裂规律,可为吲唑酰胺类合成大麻素的结构推断与鉴定提供参考。     

合成大麻素类新精神活性物质检验方法研究进展

近几年,合成大麻素类新精神活性物质备受关注。合成大麻素可在人体内模拟四氢大麻酚发挥作用,同时还具有易用性、难被检测等特点,在世界范围内被越来越多人非法使用,严重影响人类身心健康。为此,各国科研人员针对合成大麻素类新精神活性物质进行了诸多相关研究。本文介绍了合成大麻素类新精神活性物质的结构、分类、毒理毒性,对其体内代谢机理和检验方法研究进展进行了综述。同时介绍了合成大麻素成分检验领域的一些新的探索思路,并对该领域的发展作了简要展望。     

超高效液相色谱法同时测定电子烟油中的5种吲哚/吲唑酰胺类合成大麻素北大核心CSCD

合成大麻素是目前世界上滥用最多的新精神活性物质之一,其结构多变,更新迅速,目前已发展至新型第八代吲哚/吲唑酰胺类。近年来与吲哚/吲唑酰胺类合成大麻素相关的案件逐渐增多,在实际案件中对缴获物中合成大麻素的定量分析需求随之增多,但相应的检验鉴定技术仍处于发展阶段。本研究针对电子烟油中5种常见的吲哚/吲唑酰胺类合成大麻素,建立了超高效液相色谱法对其同时进行定量分析测定。实验对流动相的种类、洗脱梯度、柱温、检测波长等色谱条件进行了优化,再结合外标法定量,实现了对5种合成大麻素的定量分析。样品用甲醇提取,在Waters ACQUITY UPLC CSH C18(100 mm×2.1 mm,1.7μm)色谱柱上进行分离,柱温35℃,流速0.3 mL/min,进样量1μL,乙腈和超纯水作为流动相进行梯度洗脱,检测波长为290 nm和302 nm。结果表明,采用该方法,5种合成大麻素可在10 min内完全分离,在1~100 mg/L范围内线性关系良好,相关系数(r^(2))均可以达到0.9999,检出限为0.2 mg/L,定量限为0.6 mg/L,满足实际样品分析需求。采用1、10、100 mg/L 3个水平的5种合成大麻素混合标准溶液进行精密度试验,日内精密度(n=6)均小于1.5%,日间精密度(n=6)均小于2.2%。以空白电子烟油为基质样品,在2、10、50 mg/L 3个加标水平下进行加标回收试验,各待测物的平均加标回收率为95.5%~101.9%,相对标准偏差(RSD,n=6)为0.2%~1.5%,准确度为-4.5%~1.9%。本方法具有准确、快速、灵敏、分离效果好等优点,适用于电子烟油中5种吲哚/吲唑酰胺类合成大麻素的定量测定,可满足相关鉴定工作的要求,也可为具有相似结构的合成大麻素的液相色谱定量分析提供参考。     

血液中吲唑酰胺类合成大麻素的检验研究

建立了血液中6种吲唑酰胺类合成大麻素超高效液相色谱-串联质谱(UPLC-MS/MS)检验方法.前处理分别采用沉淀蛋白和固相萃取2种方法,UPLC-MS/MS检测,选用ACQUITY UPLC BEH C18(1.7 μm,2.1 mm ×100 mm)色谱柱,含1 mmol/L甲酸铵的甲酸-水(1∶1000,V∶V)溶...     

气相色谱-质谱联用法同时测定"电子烟油"中9种吲唑类新型合成大麻素

针对“电子烟油”中的吲唑类新型合成大麻素物质,建立了气相色谱－质谱联用（GC－MS）分析方法。以地西泮为内标物,待测样本经甲醇提取后,采用HP－5MS色谱柱（30 m × 0.25 mm × 0.25 μm）,设置起始温度200 ℃（保持1 min）,以20 ℃/min升至260 ℃（保持1 min）,再以5 ℃/min升至300 ℃（保持10 min）的程序升温条件对9种吲唑类合成大麻素同时进行定性和内标法定量检测,并对目标物的质谱碎片碎裂方式进行解析。结果表明,9种目标物质在20 min内得到有效分离,并在1.0～100.0 μg/mL范围内呈良好的线性关系,相关系数（r2）均大于0.997,检出限和定量下限分别为0.04～0.25 μg/mL和0.15 ~ 0.85 μg/mL;加标回收率为95.1%～104%,日内相对标准偏差（RSD）均小于4.6%,日间RSD均小于8.4%。该方法快速、准确,灵敏度高,适用于实际案件检验。     

缴获电子烟油样品中75种合成大麻素的1H qNMR定量分析研究

通过考察75种合成大麻素（SCRAs）的关键定量参数,首次建立了可用于电子烟油样品中75种SCRAs定量分析的核磁共振氢谱定量分析方法（1H qNMR）。以1,3,5-三甲氧基苯为内标,将烟油样品经氘代甲醇稀释后直接进行分析。方法的定量下限为0.03%（质量分数）,日内相对标准偏差（RSD）小于0.90%,日间RSD小于1.5%,基质加标回收率为93.3%～100%。采用1H qNMR法对19份缴获烟油样品中的4种合成大麻素3,3-二甲基-2-[1-(5-氟戊基)吲唑-3-甲酰氨基]丁酸甲酯（5F-ADB）、2-[1-(5-氟戊基)-1H-吲哚-3-甲酰氨基]-3,3-二甲基丁酸甲酯（5F-MDMB-PICA）、2-[1-(4-氟丁基)-1H-吲唑-3-甲酰氨基]-3,3-二甲基丁酸甲酯（4FMDMB-BUTINACA）、N-(1-氨基-3,3-二甲基-1-氧代丁-2-基)-1-丁基-1H-吲唑-3-甲酰胺（ADB-BUTINACA）进行定量分析,得到其含量范围为0.072%～2.056%。19份烟油样品的1H qNMR定量结果与高效液相色谱法定量结果无显著性差异。该研究所建立的电子烟...     

超高效液相色谱-高分辨质谱法检验4种酰胺类合成大麻素同分异构体

同分异构现象在合成大麻素中普遍存在，因其结构与性质上的差异并不显著，当同时存在时分离鉴定较为困难，为公安实践中合成大麻素的检验鉴定带来了一定的挑战。本研究利用超高效液相色谱-高分辨质谱技术(UHPLC-HRMS)建立了5F-EMB-PICA与5F-MDMB-PICA、ADB-BINACA与AB-PINACA这2对酰胺类合成大麻素同分异构体的检验方法。选用Hypersil GOLD C₁₈色谱柱(100 mm×2.1 mm, 1.9μm)进行UHPLC分离，以含0.1%甲酸的甲醇溶液和含10 mmol/L甲酸铵的0.1%甲酸水溶液为流动相进行梯度洗脱。高分辨质谱采用一级质谱全扫描/数据依赖二级质谱扫描(Full MS/dd-MS²)进行检验。结果表明，采用上述仪器条件，能够实现4种合成大麻素同分异构体的分离分析，5F-EMB-PICA和5F-MDMB-PICA的分离度为2.06, ADB-BINACA和AB-PINACA的分离度为1.22,均达到了有效分离的目的。研究进一步开展了方法学指标考察，5F-EMB-PICA、5F-MDMB-PICA、...     

苯基异丙基-酰胺系列合成大麻素质谱特征的研究

采用气相色谱-质谱联用(GC-MS)法和超高效液相色谱-串联四极杆飞行时间质谱(UPLC-QTOF-MS)法对新一代合成大麻素苯基异丙基(CUMYL)-酰胺系列化合物进行分析。GC-MS分析采用Aglient DB-5MS石英毛细管色谱柱(30 m×0.25 mm×0.25μm),以140℃为初温进行程序升温,在电子轰击源(EI)模式下采集数据;UPLC-QTOF-MS分析采用Waters Acquity UPLC BEH C₁₈色谱柱(100 mm×2.1 mm, 1.7μm),以0.1%甲酸(A)-乙腈(B)为流动相进行梯度洗脱,在电喷雾正离子(ESI⁺)-碰撞诱导解离(CID)模式下采集数据。通过总结此类物质在两种模式下获得的碎片离子与分子结构的关系,推测其可能的碎裂途径,并归纳了通过特征性离子快递筛查未知CUMYL-酰胺系列合成大麻素的方法,为此类物质的鉴定提供了参考。     

新型含异噁唑单元的吡唑酰胺类衍生物的合成及杀虫活性

运用活性亚结构拼接的原理,以杀虫剂氯虫苯甲酰胺为先导结构,引入异噁唑环单元,合成了16个含异噁唑环取代的新型吡唑酰胺化合物,采用¹H NMR、¹³C NMR、元素分析等方法对其目标物的结构进行了表征.初步生物活性测试数据显示,大多数化合物在500μg/m L浓度下对粘虫呈现出100%的杀死率.其中3个化合物在100μg/m L浓度下对粘虫的杀死率达80%～100%,在浓度降至20μg/m L时,3个化合物对粘虫仍表现出40%～50%的杀虫活性.3个化合物在500μg/m L浓度下对蚜虫显示出100%的杀虫效果,在100μg/m L浓度下对蚜虫仍有70%～100%的杀虫活性.另外2个化合物在500μg/m L时对朱砂叶螨的防效为90%～100%.     

新型异噁唑山酮素骨架螺环氧化吲哚类化合物的合成

本文以色酮-氧化吲哚合成子(1)与硝基异噁唑苯乙烯(2),催化剂DBU作用下,经分子间Michael加成,分子内Michael加成环化反应,获得7个新型异噁唑山酮素骨架螺环氧化吲哚类化合物3a~3g,产率87%~93%,dr=8/1~15/1, 其结构经¹H NMR, ¹³C NMR和HR-MS（ESI-TOF）表征。      

Separation of isomers of new psychoactive substances and isotope-labeled amphetamines using UHPSFC-MS/MS and UHPLC-MS/MS

The use of sub-2?µm particles columns is finding its use in ultrahigh-pressure supercritical fluid chromatography (UHPSFC), opening up for fast analysis and high-resolution separations. The development of new and more robust systems also makes the technique more interesting for bioanalytical analysis, where the need for reproducible and fast analysis with little downtime is great. One area where the use of UHPSFC could become a useful tool is in the separation of structural isomers of new psychoactive substances (NPS). 2-, 3-, and 4- structural isomers of fluoroamphetamine, fluoromethamphetamine, and methylmethcathinone, isomeric pairs of the synthetic cannabinoids UR-144/UR-144 degradant, XLR-11/XLR-11 degradant, JWH-015/JWH-073, and JWH-019/JWH-122, as well as amphetamine and several stable isotope-labeled amphetamine internal standards were separated with UHPSFC-MS/MS and compared with ultrahigh-pressure liquid chromatography (UHPLC) MS/MS. NPS isomers that were difficult to separate with reversed-phase UHPLC-MS/MS were separated by UHPSFC; in most cases with an orthogonal retention order to UHPLC. In contrast to the behavior seen when using reversed-phase UHPLC, the deuterated amphetamines eluted later than amphetamine with UHPSFC. ¹³C₆-labeled amphetamine coeluted with amphetamine for all conditions, making this the best choice of an internal standard.     

Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in ‘herbal mixtures’ using LC‐MS/MS techniques

Herbal mixtures, such as ‘Spice’, containing cannabimimetic compounds are easily available on the Internet and have become increasingly popular among people having to undergo urine drug testing, as these compounds are not detected by current immunochemical tests. For analysis of urine samples, knowledge of the main metabolites is necessary as the unchanged compounds are usually not found in urine after consumption. In this paper, the identification of the major metabolites of the currently most common seven synthetic cannabinoids is presented. Urine samples from patients of psychiatric facilities known to have consumed synthetic cannabinoids were screened by LC‐MS/MS and HR‐MS/MS techniques, and the major metabolites for each of the following synthetic cannabinoids were identified by their enhanced product ion spectra and accurate mass measurement: JWH‐018, JWH‐073, JWH‐081, JWH‐122, JWH‐210, JWH‐250 and RCS‐4. The major metabolic pathway is monohydroxylation either at the N‐alkyl side chain, the naphthyl moiety or the indole moiety. In addition, metabolites with carboxylated alkyl chains were identified for some of the compounds. These results facilitate the design of urine screening methods for detecting consumption of synthetic cannabinoids. Copyright © 2012 John Wiley & Sons, Ltd.     

六方相NaYF4:Yb/Er纳米晶制备方法研究进展

综述了六方相NaYF4:Yb/Er纳米晶的制备方法,着重总结了三氟乙酸盐热分解法、共沉淀法、碳酸盐热分解法、离子热法、水热法及两步法的研究进展,并就其发展前景进行了展望.     

Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantitation of synthetic cannabinoids of the aminoalkylindole type and methanandamide in serum and its application to forensic samples

After the discovery of synthetic cannabimimetic substances in 'Spice'-like herbal mixtures marketed as 'incense' or 'plant fertilizer' the active compounds have been declared as controlled substances in several European countries. As expected, a monitoring of new herbal mixtures which continue to appear on the market revealed that shortly after control measures have been taken by legal authorities, other compounds were added to existing mixtures and to new products. Several compounds of the aminoalkylindole type have been detected so far in herbal mixtures but still their consumption cannot be detected by commonly used drug-screening procedures, encouraging drug users to substitute cannabis with those products. There is a increasing demand on the part of police authorities, hospitals and psychiatrists for detection and quantification of synthetic cannabinoids in biological samples originating from psychiatric inpatients, emergency units or assessment of fitness to drive. Therefore, a liquid chromatography-tandem mass spectrometry method after liquid-liquid extraction for the quantitation of JWH-015, JWH-018, JWH-073, JWH-081, JWH 200, JWH-250, WIN 55,212-2 and methanandamide and the detection of JWH-019 and JWH-020 in human serum has been developed and fully validated according to guidelines for forensic toxicological analyses. The method was successfully applied to 101 serum samples from 80 subjects provided by hospitals, detoxification and therapy centers, forensic psychiatric centers and police authorities. Fifty-seven samples or 56.4% were found positive for at least one aminoalkylindole. JWH-019, JWH-020, JWH-200, WIN 55,212-2 and methanandamide were not detected in any of the analyzed samples.     

MEKC–MS/MS method using a volatile surfactant for the simultaneous determination of 12 synthetic cannabinoids

This study describes a method for the simultaneous determination of 12 synthetic cannabinoids by MEKC–MS/MS using a volatile surfactant (ammonium perfluorooctanoate) as a constituent of the micellar pseudostationary phase. Although most synthetic cannabinoids comigrated by a CZE method, sufficient separation could be achieved by the proposed method. The best separation was made possible by 50 mM ammonium perfluorooctanoate in 20% v/v acetonitrile/water (apparent pH* 9.0) as the BGE, followed by MS detection using a sheath liquid composed of 5 mM ammonium formate in 50% v/v methanol/water mixed hydro‐organic solvent. The standard calibration curve for all analytes showed good linearity (r > 0.99). Satisfactory recoveries, ranging from 89.5 to 101.7%, were obtained. The LODs were 6.5–76.5 μg/g for the target analytes. This method appears to be a useful tool for the identification of synthetic cannabinoids in illegal herbal incense blends.     

Analysis of 30 synthetic cannabinoids in serum by liquid chromatography‐electrospray ionization tandem mass spectrometry after liquid‐liquid extraction

The analysis of synthetic cannabinoids in human matrices is of particular importance in the fields of forensic and clinical toxicology since cannabis users partly shift to the consumption of ‘herbal mixtures’ as a legal alternative to cannabis products in order to circumvent drug testing. However, comprehensive methods covering the majority of synthetic cannabinoids already identified on the drug market are still lacking. In this article, we present a fully validated method for the analysis of 30 synthetic cannabinoids in human serum utilizing liquid‐liquid extraction and liquid chromatography‐electrospray ionization tandem mass spectrometry. The method proved to be suitable for the quantification of 27 substances. The limits of detection ranged from 0.01 to 2.0 ng/mL, whereas the lower limits of quantification were in the range from 0.1 to 2.0 ng/mL. The presented method was successfully applied to 833 authentic serum samples during routine analysis between August 2011 and January 2012. A total of 227 (27%) samples was tested positive for at least one of the following synthetic cannabinoids: JWH‐018, JWH‐019, JWH‐073, JWH‐081, JWH‐122, JWH‐200, JWH‐203, JWH‐210, JWH‐307, AM‐2201 and RCS‐4. The most prevalent compounds in positive samples were JWH‐210 (80%), JWH‐122 (63%) as well as AM‐2201 (29%). Median serum concentrations were all below 1.0 ng/mL. These findings demonstrate a significant shift of the market of synthetic cannabinoids towards substances featuring a higher CB₁ binding affinity and clearly emphasize that the analysis of synthetic cannabinoids in serum or blood samples requires highly sensitive analytical methods covering a wide spectrum of substances. Copyright © 2012 John Wiley & Sons, Ltd.     

Positional isomer differentiation of synthetic cannabinoid JWH‐081 by GC‐MS/MS

Like many new designer drugs of abuse, synthetic cannabinoids (SC) have structural or positional isomers which may or may not all be regulated under law. Differences in acute toxicity may exist between isomers which impose further burden in the fields of forensic toxicology, medicine and legislation. Isomer differentiation therefore becomes crucial from these standpoints as new designer drugs continuously emerge with just minor positional modifications to their preexisting analogs. The aim of this study was to differentiate the positional isomers of JWH‐081. Purchased standard compounds of JWH‐081 and its positional isomers were analyzed by gas chromatography‐electron ionization‐mass spectrometry (GC‐EI‐MS) first in scan mode to investigate those isomers who could be differentiated by EI scan spectra. Isomers with identical or near‐identical EI spectra were further subjected to GC‐tandem mass spectrometry (MS/MS) analysis with appropriate precursor ions. EI scan was able to distinguish 3 of the 7 isomers: 2‐methoxy, 7‐methoxy and 8‐methoxy. The remaining isomers exhibited near‐identical spectra; hence, MS/MS was performed by selecting m/z 185 and 157 as precursor ions. 3‐Methoxy and 5‐methoxy isomers produced characteristic product ions that enabled the differentiation between them. Product ion spectrum of 6‐methoxy isomer resembled that of JWH‐081; however, the relative ion intensities were clearly different from one another. The combination of EI scan and MS/MS allowed for the regioisomeric differentiation of the targeted compounds in this study. Copyright © 2015 John Wiley & Sons, Ltd.     

芳香偶氮化合物的合成研究进展

综述了芳香偶氮化合物的主要合成方法,包括重氮偶联反应、米尔斯反应、胺的氧化、芳肼的的氧化、硝基化合物的还原偶联反应、重氮盐的二聚反应、叠氮化合物的热解等,并对各方法的优缺点进行了简要评述。     

Characterization and catalytic behavior of Na-W-Mn-Zr-S-P/SiO2 prepared by different methods in oxidative coupling of methane

Na-W-Mn-Zr-S-P/SiO2 catalysts for oxidative coupling of methane (OCM) were prepared by incipient wetness impregnation, sol-gel and mixture slurry methods. The catalyst prepared by mixture slurry method showed the best catalytic performance among all samples. In addition, the effects of different addition sequences of Na, W, Mn, Zr, S and P on the catalytic performance were studied. The absence of Na before the addition of Mn and Zr in the catalysts preparation depressed the formation of the active phases of Mn2O3 and ZrO2 and decreased the activities of the catalysts significantly.