A 'cold synthesis' of heroin and implications in heroin signature analysis utility of trifluoroacetic/acetic anhydride in the acetylation of morphine

Treatment of morphine, at room temperature, with a mixture of trifluoroacetic anhydride (TFAA) and acetic acid (20-30min) affords good yields of heroin. GC-MS and HPLC examination shows that heroin produced by this route to be extremely clean, but the product contains slightly less heroin than observed via the more traditional acetic anhydride (AA) route (76.1% versus 83.55%); and greater quantities of 3-MAM and 6-MAM (6.9% versus 0.75% and 7.13% versus 0.63%). The concentration ratios of the major alkaloid impurities were found to be both production method (TFAA and AA) as well as morphine extraction methodology dependant. Data contained herein describe the impact of this new production method on current intelligence efforts, largely by-passing existing heroin signature programs and the UNDCP's efforts to restrict access to key synthetic precursors. Given the methodology dependency we find that examination of the major alkaloid ratios is unsuitable for the development of a new heroin signature program. Further examination of the TFAA methodology allowed the identification of TFAA specific marker compounds, namely bis-trifluoroacetylmorphine (30), 3-trifluoroacetyl-6-acetylmorphine (31), 3-acetyl-6-trifluoroacetylmorphine (32) and trifluoroacetylcodeine (33). However, the hydrolytic lability of trifluroacetyl esters requires careful treatment of suspect samples, thus we propose a modification to existing HSP's in instances were the 6-MAM/WM ratio falls within the average minimum and maximum values of 6.17 and 17.32.     

Signature Profiling and Classification of Illicit Heroin by GC-MS Analysis of Acidic and Neutral Manufacturing Impurities

Abstract:  The illicit manufacture of heroin results in the formation of trace level acidic and neutral impurities. These impurities are detectable in illicit heroin and provide valuable information about the manufacturing process used. The isolation, derivatization, and semiquantitative analysis of neutral and acidic heroin manufacturing impurities by programmed temperature vaporizing injector-gas chromatography-mass spectrometry (PTV-GC-MS) is described. Trace acidic and neutral heroin impurities were isolated from basic fractions using liquid–liquid extraction. Extracted impurities were treated with N -Methyl- N -trimethylsilyltrifluoroacetamide followed by PTV-GC-MS analyses. Semiquantitative data were obtained using full scan mass spectrometry utilizing unique ions or ion combinations for 36 trace impurities found in crude and/or highly refined heroin samples. Minimum detection limits for acidic and neutral impurities were estimated to be at the 10⁻⁷ level relative to total morphine. Over 500 authentic heroin samples from South America, Mexico, Southwest Asia, and Southeast Asia were analyzed. Classification of illicit heroin based on the presence or absence and relative amounts of acidic and neutral impurities is presented.     

Impurities, adulterants and diluents of illicit heroin in Denmark (Jutland and Funen)

The contents of impurities, adulterants and diluents in 77 samples of illicit heroin were determined by a combination of high-performance liquid chromatography and gas chromatography. The origin of each sample was characterized by calculating the content of the opium alkaloids in relation to the heroin content. The routes of distribution were compared by determination of the contents of caffeine, procaine and sugars. The results were used as a "chemical fingerprint" of each sample. The results indicate that it is difficult to prove, with certainty, that two samples are identical. However, in most cases, by determining the amounts of impurities, adulterants and diluents in heroin samples, it will be possible to ascertain whether two samples are different and, in many cases, to determine with reasonable certainty whether two samples are identical.     

Chemical profiling of heroin recovered from the North Korean merchant vessel Pong Su

Heroin samples, seized from the North Korean merchant vessel Pong Su in Australian waters, were analyzed to determine geographic origin. Duplicate samples were analyzed by the National Measurement Institute's Australian Forensic Drug Laboratory and the United States Drug Enforcement Administration's Special Testing and Research Laboratory. Alkaloid ratios were determined by both liquid chromatography-diode array detection (LC-DAD) and capillary electrophoresis-diode array detection (CE-DAD) techniques. Acid/neutral manufacturing by-products were determined by solvent extraction followed by gas chromatography-mass spectrometry (GC-MS). Solvents, trapped in the heroin particles during manufacture, were detected by both static headspace GC-MS and purge and trap GC-MS. The alkaloid ratios obtained were consistent with heroin of a Southeast Asian (SEA) origin and principal component analysis of the alkaloid results demonstrated the presence of at least four subgroupings within the seizure. The solvent analysis detected diethyl ether and ethyl acetate, solvents typically seen in SEA heroin. However, the acid/neutral analysis revealed compounds not normally seen in heroin of a SEA origin. Furthermore, sterol-like molecules, always detected in the acid/neutral analysis of SEA heroin, were absent from the Pong Su samples. The Pong Su heroin, although similar to SEA heroin, has sufficient differences to classify it as having an unknown origin at the time of this writing.     

Geographic origin determination of heroin and cocaine using site-specific isotopic ratio deuterium NMR

SNIF-NMR (Site-specific natural isotopic fractionation measured by deuterium NMR) was employed on 36 heroin samples from seven different known origins, and two cocaine samples from two different known origins. Heroin has two "synthetic" deuterium labeled sites (the two acetyls from acetic anhydride, each representing three equivalent nuclei) and 15 "natural" deuterium labeled sites (originating from the morphine produced in the opium plant). The "natural" sites have the potential for determining geographic location of the original opium plant, while the "synthetic" sites could assist in giving information about the commercial source of acetic anhydride used to convert morphine to heroin. Cocaine has 15 "natural" deuterium labeled sites. This study shows that SNIF-NMR has some use in determining the geographic origin of heroin and also has good potential for determining the geographical origin of cocaine.     

Isolation and identification of unique marker compounds from the Tasmanian poppy Papaver somniferum N. Implications for the identification of illicit heroin of Tasmanian origin

Tasmanian opium accounts for 25% of the world's legal supply of opium straw, and in 1998-99 sufficient numbers of flower pods (66,013) to manufacture ca 500 kg of heroin were stolen. Whilst the heroin signature program has been developed to determine the origin of heroin from other key producers, no such signature currently exists for Tasmanian derived heroin. Tasmanian poppies contain a unique alkaloid, oripavine, which is the source of 'marker' impurities in illicit heroin produced from Tasmanian poppy straw. Treatment of oripavine (500mg) under Thiboumery and Mohr heroin processing conditions, followed by simple evaporative workup afforded 613 mg of a dark orange residue, which upon extensive chromatographic purification yielded oripavine 3-acetate (2) 22 mg; 3-acetyl-N-acetyldesthebaine (3) 35 mg; 3-acetyl-6-methoxy-4,5-epoxyphenanthrene (4) 5.8 mg; 3,4-diacetyl-6-methoxyphenanthrene (5) 27 mg; and 3,4,6-methoxy-5-[2(N-methylacetamido)]ethylphenanthrene (6) 52 mg. Compounds (2-6) are derived from oripavine and are unique to heroin derived from the Tasmanian poppy Papaver somniferum N. Analysis of illicit heroin samples seized from Turkey, Pakistan, Columbia and Myanmar did not reveal any of the aforementioned marker compounds. We have, however, identified four of these marker compounds (3-6) in seized heroin samples from Australia suggesting that they are of Tasmanian origin. Complete details of the isolation and identification of these compounds are provided.     

Quantitative determination of amphetamines, cocaine, and opiates in human hair by gas chromatography/mass spectrometry

Hair of young subjects (N = 36) suspected for drug abuse was analysed for morphine, codeine, heroin, 6-acetylmorphine, cocaine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). The analysis of morphine, codeine, heroin, 6-acetylmorphine, cocaine, and methadone in hair included incubation in methanol, solid-phase extraction, derivatisation by the mixture of propionic acid anhydride and pyridine, and gas chromatography/mass spectrometry (GC/MS). For amphetamine, methamphetamine, MDA, MDMA, and MDEA analysis, hair samples were incubated in 1M sodium hydroxide, extracted with ethyl acetate, derivatised with heptafluorobutyric acid anhydride (HFBA), and assayed by GC/MS. The methods were reproducible (R.S.D. = 5.0-16.1%), accurate (85.1-100.6%), and sensitive (LoD = 0.05-0.30ng/mg). The applied methods confirmed consumption of heroin in 18 subjects based on positive 6-acetylmorphine. Among these 18 heroin consumers, methadone was found in four, MDMA in two, and cocaine in two subjects. Cocaine only was present in two, methadone only in two, methamphetamine only in two, and MDMA only in seven of the 36 subjects. In two out of nine coloured and bleached hair samples, no drug was found. Despite the small number of subjects, this study has been able to indicate the trend in drug abuse among young people in Croatia.     

体内海洛因代谢产物的分析研究

本文介绍了从海洛因成瘾者尿中提取净化和定性定量分析海洛因主要代谢产物单乙酰吗啡和吗啡的方法．阳性尿以乙基吗啡为内标．水解后液－液提取或液－固提取，经衍生化后采用ＧＣ／ＭＳ，ＧＣ／ＦＩＤ，ＧＣ／ＮＰＤ法分析，方法简便、准确、灵敏、重现性好．应用本法对八十余例吸毒成瘾者尿样进行测定，取得了令人满意的结果．     

Four new illicit cocaine impurities from the oxidation of crude cocaine base: formation and characterization of the diastereomeric 2,3-dihydroxy-3-phenylpropionylecgonine methyl esters from cis- and trans-cinnamoylcocaine

Four new impurities have recently been detected in the gas chromatographic signature profiles of many illicit cocaine hydrochloride exhibits. These impurities are only seen in exhibits that have been oxidized and are most prominent in samples that have been highly oxidized. Exhibits containing these compounds were subjected to gas and liquid chromatographic-mass spectrometric analyses to determine the identity of the impurities. These impurities were subsequently synthesized to verify their structures. Four diastereomeric diols formed from the oxidation of cis- and trans-cinnamoylcocaine were characterized by nuclear magnetic resonance spectrometry, mass spectrometry, and synthesis. Oxidation of cis-cinnamoylcocaine in neutral conditions yielded (2R,3R)-dihydroxy-3-phenylpropionylecgonine methyl ester and (2S,3S)-dihydroxy-3-phenylpropionylecgonine methyl ester, while trans-cinnamoylcocaine produced (2R,3S)-dihydroxy-3-phenylpropionylecgonine methyl ester and (2S,3R)-dihydroxy-3-phenylpropionylecgonine methyl ester. The recent appearance of these new impurities suggests that some illicit cocaine processors have modified their oxidation procedures of crude cocaine base for transformation into illicit refined cocaine hydrochloride.     

GC/MS determination of pyrolysis products from diacetylmorphine and adulterants of street heroin samples

The inhalation of heroin vapors after heating on aluminium foil ("chasing the dragon") is gaining popularity nowadays among heroin users seeking to avoid the risks of parenteral drug administration. The heroin-smoking procedure was simulated under laboratory conditions by heating the samples on aluminium foil at 250 to 400 degrees C and collecting the vapors in a condenser trap. A total of 72 pyrolysis products of diacetylmorphine, street heroin, residues from aluminium foils used to smoke street heroin, typical by-products, and adulterants were detected by gas chromatography/mass spectrometry (GC/MS). About half of these compounds could be identified. Diacetylmorphine (base and salt) undergoes substantial to complete degradation. Some typical street heroin constituents, like morphine, codeine, acetylcodeine, papaverine, and caffeine, are rather heat-stable. Other compounds, like noscapine and paracetamol, are pyrolyzed to a greater extent. The principal chemical reactions leading to the formation of pyrolysis products are desacetylation, transacetylation, N-demethylation, O-methylation, ring cleavage and oxydation.     

The detection of acetylcodeine and 6-acetylmorphine in opiate positive urines

Acetylcodeine (AC), an impurity of illicit heroin synthesis, was investigated as a urinary biomarker for detection of illicit heroin use. One hundred criminal justice urine specimens that had been confirmed positive by GC/MS for morphine at concentrations >5000 ng/ml were analyzed for AC, 6-acetylmorphine (6AM), codeine, norcodeine and morphine. The GC/MS analysis was performed by solid phase extraction and derivatization with propionic anhydride. Total codeine and morphine concentrations were determined by acid hydrolysis and liquid/liquid extraction. AC was detected in 37 samples at concentrations ranging from 2 to 290 ng/ml (median, 11 ng/ml). 6AM was also present in these samples at concentrations ranging from 49 to 12 600 ng/ml (median, 740 ng/ml). Of the 63 specimens negative for AC, 36 were positive for 6AM at concentrations ranging from 12 to 4600 ng/ml (median, 124 ng/ml). When detected, the AC concentrations were an average of 2.2% (0.25 to 10.2%) of the 6AM concentrations. There was a positive relationship between AC concentrations and 6AM concentrations (r=0.878). Due to its very low concentration in urine, AC was found to be a much less reliable biomarker for illicit heroin use than 6AM in workplace or criminal justice urine screening programs. However, AC detection could play an important role in determining if addicts in heroin maintenance programs are supplementing their supervised diacetylmorphine doses with illicit heroin.     

The detection of 6-monoacetylmorphine in urine, serum and hair by GC/MS and RIA

6-Monoacetylmorphine (6-MAM) is a good indicator for the intake of heroin and can be detected in blood, urine and hair of heroin users. A new radioimmunoassay (RIA) designed specifically for 6-monoacetylmorphine (6-MAM) was tested for its usefulness for the quantitation of the drug in urine, serum and hair. Its cross-reactivity with heroin and its metabolites, and related compounds was also determined. Eighty-nine hair, six serum and 25 urine samples where 6-MAM had been previously identified by GC/MS were analysed for 6-MAM with the new RIA kit. A good correlation existed between the GC/MS and RIA results for the hair samples. However, the amount of 6-MAM found in serum and urine differed considerably between the two methods. This difference could be explained by the cross-reactivity of the antibody with morphine and morphine-6-glucuronide, which are present in much larger amounts in serum and urine, than in hair. To evaluate a new rationalisation procedure, some hair samples were split into two portions after incubation. One part was analyzed for 6-MAM by RIA, and the other portion by GC/MS.     

GC/MS研究海洛因代谢物在吸毒者体内的分布

应用GC／MS－SIM测定了海洛因代谢物吗啡在两例海洛因延缓死亡者的体内分布,并分析了收集到的7例案子的毛发（头发、腋毛和阴毛）中6-单乙酰吗啡和吗啡含量。生物检材和毛发经酸水解、提取、醋酸酐或双（三甲基硅基）三氟乙酰胺（BSTFA）衍生化,然后进行GC／MS-SIM分析。结果表明尿、胆汁和肝脏是判定死者是否曾使用海洛因的最佳检材;毛发分析与生物检材相比有其独特的优点,可提供数月甚至数年的用药情况。为公安司法机关打击吸毒、惩治犯罪提供更可靠、有效的证据。     

Changes in place of origin of heroin seized in Denmark from 1981 to 1986. "Chemical fingerprint" of 138 samples

Hundred thirty-eight samples of heroin weighing more than 0.1 g seized between 1981 and 1986 were characterized according to their contents of opium alkaloids, adulterants, and diluents together with their form and color. The "chemical fingerprint" was used to establish a change in the heroin during the period. As compared to the first few years covered by the survey, a predominant number of the samples at the end of the period were in the base form and contained the opium alkaloids papaverine and noscapine. In particular, the concentration of noscapine as related to the heroin content of each sample had increased considerably, indicating Pakistan or Iran as being the places of origin of most of the heroin seized in Denmark at the end of the period.     

4-Dimethylaminopyridine as a catalyst in heroin synthesis

In this paper, we describe an acetylating method for fast synthesis of heroin from morphine in the presence of 4-dimethylaminopyridine (4-DMAP) as a catalyst. In the reaction which led to heroin formation, the morphine base was subjected to a solution made up of 4-DMAP (catalyst), methylene chloride (solvent) and acetic anhydride (acetylating agent). We showed that in comparison with classic acetylating procedures, reaction time can be reduced from at least several hours at elevated temperatures to <10 min at room temperature. In general, reaction time is dependent on the molar concentration ratio between morphine and 4-DMAP.     

Analysis of a simulated heroin distribution chain by HPLC

A heroin distribution chain was simulated by taking three different seizures and preparing four additional samples from each seizure by adding a paracetamol-caffeine mixture in varying amounts, resulting in three different batches each composed of five samples. All of the samples from the three batches were analyzed using HPLC with a UV-PDA detector at a wavelength of 230 nm. The area ratio of various opium alkaloids, acetylation products and components were compared. From the results of the UV area ratios, the fifteen samples could readily be separated into three batches of five samples, with each batch of five samples having a common origin.     

海洛因样本的地理来源判断

目的对在中国境内缴获的海洛因样本进行地理来源判断。方法采用气质联用技术(GC/MS)对890份海洛因样本进行了生物碱定量检测,并利用生物碱之间的相对比率建立了二维数学模型。结果将所检测的890份海洛因样本划分成3个区域,并对这3个区域中的海洛因来源进行了判断,同时讨论了含量和掺假剂等分布情况。结论实现了对中国境内缴获的海洛因样本进行地理来源推断的目的。     

超声辅助固相萃取-HPLC法测定不同地区缴获鸦片样品中生物碱

目的本文建立了超声辅助固相萃取-HPLC法定量测定缴获鸦片样品中吗啡、可待因、蒂巴因、罂粟碱、那可汀5种生物碱并同时检出6种未知化合物的方法。采用主成分分析法区分不同地区缴获的鸦片样品。方法采用超声辅助固相萃取法提取生物碱,XDB-C18（5μm×4.6mm×250mm）色谱柱,流动相为10mM的1-庚烷磺酸钠（pH 3.2）和乙腈,梯度洗脱,紫外检测器检测。结果该方法的定量限为0.58~2.78 mg/kg。添加水平在0.2～1.5mg/mL范围内,平均加标回收率为81.0%～99.2%,相对标准偏差为1.6%～5.0%。结论本方法重现性好、定量准确,满足定量检测鸦片中生物碱含量并对不同产地鸦片进行分类的需要。     

Component analysis of illicit heroin samples with GC/MS and its application in source identification

A novel method based on GC/MS and GC for component analyses of seized illicit heroin was established by using SKF525A as an internal standard. The main components in illicit heroin products such as heroin, O3-acetylmorphine, monoacetylcodeine, and O6-acetylmorphine were determined quantitatively and the organic adulterants such as paracetamol, acetaminophen caffeine and theophylline were detected qualitatively using the developed method. With these obtained data, 500 seized illicit heroin samples were divided into nine groups. The decomposition pattern of heroin was studied. The dependencies of both the decomposition pattern and the content ratios of monoacetylcodeine to heroin and monoacetylcodeine to O6-acetylmorphine on the source of the seized illicit heroin were observed. This information was used to develop a novel method for its source identification. The examination results were in agreement with the practical cases, thus providing significant information for detection of criminal cases involving illicit heroin.     

Alkaloid content of the seeds from Erythroxylum Coca var. Coca

Alkaloid extracts from the seeds of Erythroxylum Coca var. Coca grown in the Chapare Valley of Bolivia were subjected to gas and liquid chromatographic-mass spectrometric analyses. Several alkaloids from these seeds were detected and characterized, including methylecgonidine, tropine, 3alpha-acetoxytropane, ecgonine methyl ester, cuscohygrine, N-norbenzoyltropine, benzoyltropine, hexanoylecgonine methyl ester, cocaine, cis-cinnamoylcocaine, and trans-cinnamoylcocaine. Methylecgonidine was determined to be the primary constituent and not an analytical artifact. Additionally, two significant new uncharacterized alkaloids were established as present. Recent evidence suggests that some cocaine processors are adding this seed extraction material to cocaine extracted from coca leaf and may impact cocaine impurity signature profiles.