毛细管气相色谱法对大麻中主要成分的定性定量分析

采用毛细管气相色谱法测定大麻中大麻酚、四氢大麻酚和大麻二酚的含量。以氯仿为提取溶剂,甲醇为色谱溶剂,用ＨＰ－５（１０ｍ×０．５３ｍｍ×２．６５μｍ）柱,以柱温２２０℃进行测定。大麻二酚、四氢大麻酚和大麻酚在２０～１２０ｍｇ／Ｌ的浓度范围内线性关系良好,ｒ分别为０．９９９４,０．９９９１和０．９９９５,回收率分别为９７．３％～１０４．０％,９７．３％～１０６．６％和９５．３％～１０２．４％,最低检测限均为０．２μｇ／ｍＬ。利用３种主要成分保留时间的良好重现性也可进行定性。方法简便、快速、准确、灵敏。     

超高效液相色谱-串联质谱法同时测定食用油中痕量的δ-9-四氢大麻酚、大麻酚和大麻二酚

建立了超高效液相色谱-串联质谱(UPLC-MS/MS)同时测定食用油中δ-9-四氢大麻酚(THC)、大麻酚(CBN)和大麻二酚(CBD)的方法。目标分析物经甲醇提取、中性氧化铝固相萃取柱净化后,采用UPLC-MS/MS分离和检测。实验以氘代四氢大麻酚(THC-D3)为内标物,采用同位素内标法定量。在3个添加水平下,目标物的平均回收率为68.0%～101.6%,相对标准偏差为7.0%～20.1%。方法检出限为0.06～0.17μg/kg,定量限为0.20～0.52μg/kg。该方法能够满足食用油中痕量四氢大麻酚、大麻酚和大麻二酚检测的需要。     

超高效液相色谱-串联质谱法同时测定食用油中痕量的δ-9-四氢大麻酚、大麻酚和大麻二酚

建立了超高效液相色谱-串联质谱(UPLC-MS/MS)同时测定食用油中δ-9-四氢大麻酚(THC)、大麻酚(CBN)和大麻二酚(CBD)的方法。目标分析物经甲醇提取、中性氧化铝固相萃取柱净化后,采用UPLC-MS/MS分离和检测。实验以氘代四氢大麻酚(THC-D3)为内标物,采用同位素内标法定量。在3个添加水平下,目标物的平均回收率为68.0%～101.6%,相对标准偏差为7.0%～20.1%。方法检出限为0.06～0.17 μg/kg,定量限为0.20～0.52 μg/kg。该方法能够满足食用油中痕量四氢大麻酚、大麻酚和大麻二酚检测的需要。     

基于超高效液相色谱-质谱联用技术对大麻植物中3种成分及化学表型分析

建立了超高效液相色谱-质谱联用(UPLC/PDA-QDa)同时对大麻植物中Δ9-四氢大麻酚(Δ9-THC)、大麻酚(CBN)和大麻二酚(CBD)进行定性与定量分析的方法.缴获的大麻植物用甲醇超声萃取, 采用甲醇(含0.1%甲酸)和超纯水为流动相, 等度洗脱, 流速为0.2 mL/min, 经Waters UPLC BEH C18柱(50 mm×2.1 mm, 1.7 μm)分离, 利用光电二极管阵列检测器(PDA)在220 nm波长下检测, 并通过质谱检测器(QDa)对目标洗脱峰进行追踪确证.在0.5~20 μg/mL浓度范围内, 3种大麻酚类化合物的质量浓度与峰面积呈良好的线性关系, R≥0.999;低、中、高添加水平的平均回收率为82%~102%, 相对标准偏差(RSD)在0.4%~4.1%之间.本方法稳定、简便、灵敏, 能够满足检测需求.根据Δ9-THC、(Δ9-THC+CBN)/CBD、Δ9-THC/CBD或CBN/CBD表型指数, 区分不同产地大麻的化学表型, 为大麻植物的检测分析和质量控制提供了有效手段.     

大麻中3种酚类成分测定专用固相萃取柱的设计与应用

大麻中的主要成分大麻二酚(CBD)、大麻酚(CBN)和Δ9-四氢大麻酚(Δ9-THC)的含量决定了其性质和应用。在液相色谱分析中,由于大麻提取液中含有较多杂质,需要净化。该文基于大麻中CBD、CBN和Δ9-THC的结构特征及样品基质组成,根据中性氧化铝、硅酸镁和石墨化炭黑的不同表面特征,考察了这3种吸附剂对大麻提取液中叶绿素、多糖、高级脂肪酸酯及重金属离子的去除率和对3种大麻酚的回收率,确定了3种吸附剂的用量分别为1.80 g、0.15 g、0.05 g混合装填成的2 g/6 mL小柱为3种大麻酚类化合物测定的专用固相萃取柱。该小柱对大麻乙酸乙酯-甲醇提取液样品中CBD、CBN和Δ9-THC的回收率分别为98.9%, 95.7%和99.2%,对叶黄素、叶绿素a和叶绿素b的去除率分别为96.3%、99.2%和95.5%,对总糖的去除率为98.5%,对脂肪酸甘油酯的去除率为96.9%,对重金属离子的平均去除率为85.4%。优化了色谱分析条件,采用Eclipse Plus C18色谱柱(50 mm×2.1 mm, 1.8 μm),在1%乙酸水溶液-乙腈(30∶70, v/v)流动相条件下等度洗脱,流速为0.5 mL/min,柱温为30 ℃,检测波长为210 nm,进样量为1 μL,在10 min内可完成样品分析。方法学考察表明,在0.5~50 mg/L范围内,CBD、CBN和Δ9-THC的液相色谱峰面积与其质量浓度呈良好的线性关系,相关系数(R²)分别为0.9983、0.9995和0.9981,检出限分别为0.45 μg/L、0.53 μg/L和0.38 μg/L,加标回收率为90.3%~97.0%、93.7%~95.6%、90.8%~96.1%,相对标准偏差(RSD)分别为2.2%~6.1%、4.1%~8.0%、2.4%~4.8%。研究结果表明,该文以中性氧化铝、硅酸镁和石墨化炭黑制作的复合型大麻酚类成分测定专用固相萃取柱在大麻植物中3种酚类化合物的测定中具有净化杂质、防止色谱柱污染的功能。由于大麻不同部位的化学成分存在差异,在后续的研究中,还要进一步考察小柱对其他杂质的去除情况,使得制备的固相萃取小柱更具有普适性。     

高效液相色谱检测大麻中Δ9-四氢大麻酚的分析方法研究

建立了大麻毒品中主要有效成分Δ9-四氢大麻酚的液相色谱分析方法.选择甲醇作为大麻植物或大麻树脂的提取溶剂.采用岛津ODS-SP型(150 mm×4.6 mm,5μm)色谱柱作为定量方法的标准柱,紫外检测器主定量波长为210 nm,辅定量波长为195 nm或220 nm.以水-乙腈为流动相进行梯度洗脱,流速1mL/min,柱温40℃,进样量10 μL.在优化条件下,△9-四氢大麻酚在0.5～ 100.0 mg/L范围内线性良好,外标法及内标法的相关系数(r2)均大于0.99999.方法的检出限(S/N≥3.3)和定量下限(S/N≥ 10)分别为0.12 mg/L和0.40 mg/L.用该方法检测某大麻树脂样本,△9-四氢大麻酚含量的不确定度评定结果为5.32％±0.17％,k=2.实验结果表明,该方法快速、灵敏、准确、可靠,适用于大麻植物及树脂的定量测定.     

工业大麻中非兴奋剂成分大麻二酚检测方法的研究进展

大麻二酚(CBD)因其具有神经保护、镇痛、抗炎、抗氧化以及抗癫痫等药理作用而受到广泛的关注。然而随着CBD正式被列入化妆品禁用原料目录，其应用受到很大影响。同时，我国目前尚未制定CBD产品的相关法律法规、标准，跨境电商平台领域的CBD产品给监管带来极大的困难和挑战。基于此，介绍了CBD的药理作用及应用，综述了CBD检测方法的研究进展，以期为CBD的规范使用、CBD制品的规范开发提供新的思路(引用文献41篇)。     

增强型脂质去除净化剂结合超高效液相色谱-串联质谱法测定食品中8种大麻素类化合物

研究在优化前处理条件及色谱分离的基础上,建立了同时测定巧克力、软糖、糕点、饼干、饮料、白酒等6种典型食品基质中8种大麻素类化合物的超高效液相色谱-串联质谱(UPLC-MS/MS)的测定方法。前处理方法中考察了不同的净化方式,采用增强型脂质去除净化剂(EMR-Lipid)解决了巧克力中复杂油脂及软糖中胶质难以去除的问题;同时净化溶液在氮吹前加入10%丙三醇甲醇溶液,解决了目前文献方法中直接氮吹对回收率影响很大的关键问题。样品以乙腈为提取溶剂,EMR-Lipid为净化剂进行净化,无水硫酸钠除水后,乙腈层加入10%丙三醇甲醇溶液100μL,氮吹至近干;采用Waters ACQUITY UPLC BEH Shield RP18色谱柱进行分离,电喷雾负离子扫描,多反应监测(MRM)模式检测,基质匹配外标法定量。方法学研究表明,四氢大麻酚、次大麻二酚、四氢大麻素、大麻萜酚在2～200 ng/mL范围内线性关系良好;大麻酚、大麻二酚、大麻二酚酸、四氢大麻酚酸A在0.4～40 ng/mL范围内线性关系良好,相关系数(r)均大于0.995;检出限和定量限分别为0.8～4μg/kg和2～10μg/kg。在...     

高效液相色谱外标工作曲线法测定大麻树脂中四氢大麻酚含量的不确定度评定

依据JJF 1059-1999《测量不确定度评定与表示》,以检测大麻树脂中四氢大麻酚含量的实验为例,评定了采用高效液相色谱外标工作曲线法进行含量测定的不确定度.建立了高效色谱外标工作曲线法测定样品含量的数学模型,分析了不确定度的来源并给出了量化结果,合成扩展不确定度为0.15％(k=2).     

膜提取气相色谱/质谱大体积进样检测海洛因吸食者尿液中的代谢物

１ 引 言 采用固相膜提取技术对尿样进行处理，用ＧＣ／ＭＳ大体积迸样方法测定海洛因吸食者尿液中的代谢物浓度，并系统考察了吗啡、单乙酞吗啡的提取回收率、线性关系等指标，所建立的方法对吗啡和单乙酰吗啡的回收率均大于８０％；最低检出限为０．０１ｍｇ／Ｌ。用代谢物特征离子与内标物特征离子峰高比测定吗啡与单乙酰吗啡的浓度，在每ｍＬ尿添加 ０．０２～５０μｇ范围内，二者均有良好的提取线性关系，并对一例海洛因滥用者的尿液进行了成功检测。２ 实验部分２．１ 主要仪器及工作条件 Autosvstem XL/TurboMass气相色谱质谱联用…     

Quantification of morphine and its major metabolites M3G and M6G in antemortem and postmortem samples

Morphine is one of the most effective agents for the control of significant pain, primarily metabolized to morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G). While M6G is a potent opioid agonist, M3G has no opioid action and seems to have a role in side‐effects caused by morphine. In this study, a reversed‐phase high‐performance liquid chromatographic method with diode‐array and electrochemical detection was developed for the simultaneous determination of morphine, M3G and M6G in antemortem and postmortem samples (plasma, whole blood, urine, liver, kidney and brain). Morphine, glucuronides and internal standard were extracted by double solid‐phase extraction and the separation was carried out with a Waters Spherisorb® ODS2 reversed‐phase column and potassium phosphate buffer (pH = 2.2)–acetonitrile containing sodium dodecyl sulfate as the mobile phase. The method proved to be specific with good linearity for all analytes in a calibration range from 1 to 600 ng/mL and proved to be accurate and have adequate precision and recovery. Limits of detection in the studied matrices were 0.4–4.5 ng/mL for morphine, 2.7–6.1 ng/mL for M3G and 0.8–4.4 ng/mL for M6G. The proposed method can be successfully applied to quantify morphine and its metabolites in several biological samples, covering the major routes of distribution, metabolism and elimination of morphine. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous determination of morphine‐6‐d‐glucuronide,morphine‐3‐d‐glucuronide and morphine in human plasma and urine by ultra‐performance liquid chromatography–tandem mass spectrometry: Application to M6G injection pharmacokinetic study

A robust ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the determination of morphine‐6‐d ‐glucuronide (M6G), morphine‐3‐d ‐glucuronide (M3G) and morphine (MOR) in human plasma and urine has been developed and validated. The analytes of interest were extracted from plasma by protein precipitation. The urine sample was prepared by dilution. Both plasma and urine samples were chromatographed on an Acquity UPLC HSS T₃ column using gradient elution. Detection was performed on a Xevo TQ‐S tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. Matrix interferences were not observed at the retention time of the analytes and internal standard, naloxone‐D5. The lower limits of quantitation of plasma and urine were 2/0.5/0.5 and 20/4/2 ng/mL for M6G/M3G/MOR, respectively. Calibration curves were linear over the concentration ranges of 2–2000/0.5–500/0.5–500 and 20–20,000/4–4000/2–2000 ng/mL for M6G/M3G/MOR in plasma and urine samples, respectively. The precision was <7.14% and the accuracy was within 85–115%. Furthermore, stability of the analytes at various conditions, dilution integrity, extraction recovery and matrix effect were assessed. Finally, this quantitative method was successfully applied to the pharmacokinetic study of M6G injection in Chinese noncancer pain patients.     

Synthesis ofN-phenyl-substituted derivatives of morphine alkaloids

A method for the preparation ofN-phenyl-substituted morphine alkaloids by treatment of the correspondingN-nor derivatives with Ph₃Bi in the presence of Cu(OAc)₂ is proposed. 17-Nor-17-phenylthebaine thus obtained can serve as a convenient starting material for the preparation of otherN-phenyl-substituted alkaloids. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 595–598, March, 1999.     

公安办案中鸦片的前处理方法研究

确定适合公安办案的鸦片样品前处理的首选方法,为鸦片类收缴毒品的提取、检测提供参考。分别采用不同前处理方法提取鸦片中吗啡组分,采用高效液相色谱法检测,依据经济成本、提取效率、回收率等多种因素选定前处理方法,并对该方法进行优化。公安办案中对于鸦片的前处理方法首选水溶解法,固相萃取法可以作为水溶解法的补充。采用优化后的水溶–固相萃取方法,国产固相萃取小柱可以得到98.7%的回收率。进口固相萃取小柱的萃取效率略优于国产柱,而国产固相萃取小柱也能够满足检测要求。     

Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.     

Quantitative gas chromatographic/mass spectrometric analysis of morphine glucuronides in human plasma by negative ion chemical ionization mass spectrometry

A sensitive and specific method for the determination of morphine glucuronides in human plasma is presented. Morphine glucuronides, namely morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), were extracted from plasma by solid-phase extraction on C(18) cartridges at pH 9.3 and derivatized to their pentafluorobenzyl ester trimethylsilyl ether derivatives. The compounds were measured by gas chromatography/negative ion chemical ionization mass spectrometry without any further purification. Using this detection mode, a diagnostic useful fragment ion at m/z 748 was obtained at high relative abundance for both target compounds. [(2)H(3)]-labeled morphine glucuronides were used as internal standards. Calibration graphs were calculated by polynomial fit within a range of 10-1280 and 15-1920 nmol l(-1) for the 6- and 3-glucuronide, respectively. At the limit of quantitation (LOQ), the inter-assay precision was 2.21% (M3G) and 2.23% (M6G) and the GC/MS assay variability was 1.8% (M3G) and 0.9% (M6G). The accuracy at the LOQ showed deviations of +4.92% (M3G) and +1.5% (M6G). The sample recovery after solid-phase extraction was 84.7% for both M3G and M6G. The method is rugged, rapid and robust and has been applied to the batch analysis of morphine glucuronides during pharmacokinetic profiling of the drugs.     

Selective extraction of morphine from biological fluids by magnetic molecularly imprinted polymers and determination using UHPLC with diode array detection

The determination of morphine concentration in the blood and urine is necessary for patients and recruitment purposes. Herein, a magnetic molecularly imprinted polymer for selective and efficient extraction of morphine from biological samples was synthesized by using a core–shell method. Fe₃O₄ nanoparticles were coated with SiO₂‐NH₂. The molecularly imprinted polymer was coated on the Fe₃O₄/SiO₂‐NH₂ surface by the copolymerization of methacrylic acid and ethylene glycol dimethacrylate in the presence of morphine as the template molecule. The morphological and magnetic properties of the polymer were investigated. Field‐emission scanning electron microscopy indicated that the prepared magnetic polymer is almost uniform. The saturation magnetization values of Fe₃O₄ nanoparticles, Fe₃O₄/SiO₂‐NH₂, and the magnetic polymer were 48.41, 31.69, and 13.02 emu/g, respectively, indicating that all the particles are superparamagnetic. Kinetics of the adsorption of morphine on magnetic polymer were well described by second‐order kinetic and adsorption processes and well fitted by the Langmuir adsorption isotherm, in which the maximum adsorption capacity was calculated as 28.40 mg/g. The recoveries from plasma and urine samples were in the range of 84.9–105.5 and 94.9–102.8%, respectively. By using the magnetic molecularly imprinted polymer, morphine can selectively, reliably, and in low concentration be determined in biological samples with high‐performance liquid chromatography and UV detection.     

A Regio‐ and Diastereoselective Anodic Aryl–Aryl Coupling in the Biomimetic Total Synthesis of (−)‐Thebaine

The biosynthesis of thebaine is based on the regioselective, intramolecular, oxidative coupling of (R)‐reticuline. For decades, chemists have sought to mimic this coupling by using stoichiometric oxidants. However, all approaches to date have suffered from low yields or the formation of undesired regioisomers. Electrochemistry would represent a sustainable alternative in this respect but all attempts to accomplish an electrochemical synthesis of thebaine have failed so far. Herein, a regio‐ and diastereoselective anodic coupling of 3′,4′,5′‐trioxygenated laudanosine derivatives is presented, which finally enables electrochemical access to (?)‐thebaine.     

A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine

Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)‐morphine that employs two key strategic cyclizations: 1) a diastereoselective light‐mediated cyclization of an O‐arylated butyrolactone to form a tricyclic cis‐fused benzofuran and 2) a cascade ene–yne–ene ring closing metathesis to forge the tetracyclic morphine core. This approach enables a short and stereoselective synthesis of morphine in an overall yield of 6.6 %.