2013 fall 9th class illegal produc약물남용, 사이버마약

Drug Abuse – 9약물남용 -9

Illegal Production (Clandestine Lab) & Impurity Profiling불법조제 , 불순물 프로 파일링

Chungnam Natl. Univ.Dept. of Forensic Sciences

충남대 과학수사학과

Aug. – Dec., 2013

최 성 운 Sungwoon Choi

1

Illegal Production 불법약물 제조의 위험성을 설명하시오

Synthesis is relatively simple & easy with several possible methods

쉽고 , 단순 - 합성 몇가지 가능 합성법 존재

with risk with flammable solvents and corrosive chemicals 가연성 , 부식성 위험

often discovered by fires and explosions 화학약품 ( 용매 ) - 화재 ,

폭발사고

로

종종 발견

Starting Materials( 출발 / 전구 / 원료물질 ) – from household products, OTC cold,

allergy

medicine 전구물질 - 감기 , 앨러지 약품 -

가정용

Maximum conversion rate – 92% (Meth synthesis) But typically 50-75% by illicit lab.

최대 92% 가능

통상 50-75% 의 수율 , 순도 불법마약조제실험실

2

Illegal Production 불법약물 제조의 위험성을 설명하시오

Ex.) 예

For Meth Production 히로뽕생산

“Red (red phosphorus) – White (ephedrine, pseudoephedrine) – Blue

적인 ( 성냥 ) 일반 감기약 - 원료 (iodine, purple)

Process”

--- Hazardous process - phosphine gas (from HI production)

extremely toxic

매우 위험한 과정 / 공정

3

Illegal Production

Synthesis Method 합성 방법 illicitly obtained 불법적으로 취득 published method 발표된 방법 “underground literature” or internet 비밀 / 지하 문헌 , 인터넷

Impure, inferior products, & variability in quality and potency 질과 효력이 크게 From: inexperienced clandestine “chemists” 무경험화학자 변화 , 떨어짐 inappropriate Lab equipment 부적절 기구 사용 비밀 실험실 lack of Lab quality control (QC) 품질관리 없음

4

O

H2N O

1-phenyl-2-propanone,P-2-P

+

formamide

HCOOH

HN

N-formylamphetamine

HCl

NH2

Amphetamine

Leuckart Reaction (Non-metal reduction)

oil liquid"fishy-amine" odour

basified, isolated, (steam) distilledand sulfate form precipitation

Amphetamine synthesis – 루카르트법 P-2-P 전구물질사용

One of the most studied method 가장 연구많이된 방법Route specific impurities identified – 특정합성 과정에기인한 불순물 N-formylAm & 4-methyl-5-phenyl pyrimidine

5

Methamphetamine Synthesis – starting materials 전구 / 출발 물질

OHHN

OHHN

OHHN Oxidation H

N

O

Methcathinoneillicit drug

Ephedrine8mg/pill OTCoral decongestantbronchodilatorsympathomimetic amine-as stimulant, appetite suppressantfrom Ephdra (마황)-Ephedra sinica

Pseudoephedrinenasal/sinus decongestant, OTCwakefulness-promoting agentvasoconstrictionsympathomimetic amine-as stimulant, in Combination with NSAID, othersfrom Ephdra (마황)-Ephedra sinica

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감기기관지확장식욕감퇴

감기콧물 - 혈관수축액티피드에 포함

Methamphetamine Synthesis – Emde method

OHHN

ClHN

HNSOCl2

or POCl3

Pd/H2

Ephedrineor Pseudoephedrine

Chloroephedrine Methamphetamine

Unstable - decomposeRarely found

mercury-aluminum amalgamor platinum oxide

Thionyl chloride to intermediate chloroephedrine – decompose during analysis to aziridines also during basic extraction 알칼리성 추출Then reduced to product

7

Methamphetamine Synthesis – Birch method 벌치 방법

OHHN

HNNH3

Li or Na metal

Ephedrine orPseudoephedrine

methamphetamine

Dissolving metal reduction (Birch reduction) - Nazi methodusually produce "clean" end-productRoute specific impurities - N-methyl-1-(1-(1,4-cyclohexadienyl))-2-propanamine

anhydrous ammoniahazardous, explosions-quite common

lithium stripsfrom batteries

Very dangerous - both alkali metal, anhydrous ammonia - highly reactive

Typical impurities – ephedrine, pseudoephedrine, 전구물질 aziridines --- not route-specific (also from Emde) dimethylnaphthalenes 남아있는 ( 출발 ) 전구물질

HN

8

Illegal Production-- 정리

9

MDMA, MDEA & MDA synthesis

O

O O

3,4-DMP

NH2

methylamine

O

O N

O

O NH

MDMA

reducingagents

OHNHCOOH

O

O N

O

N-methylformamide

HCl

MDMA

Leuckart Method

Reductive amination

MDMA – usually a white crystalline substance, pressed into a small pillBrownish tint to the tablets or powder 갈색 색상띈 정제 , 가루 - -Incomplete synthesis 불완전 합성의미

Other substances found in pill-Am, ephedrine, caffeine, ketamine, Meth, acetaminophen, MDA, MDEA, PMA, dextromethorphan, etc.

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MDMA, MDEA & MDA synthesis

O

O

CHO

Piperonalnatural minor extractof vanilla

O

O

O

O

Safrole Isosafrole

sassafras oil, other safrole-richessential oil, plant parts

EtNO2R-NH2 (amine)

O

O NO2

O

O NH2

reduction

MDA

O

O O

3,4-DMP-2-P3,4-methylenedioxyphenyl-2-propanone

MDMA

Key precursor: 3,4-DMP-2-PSafrole- commercially availableEthylamine – MDEAmmonia – MDA

Nitropropene method – 1990s piperonal+nitroethane

11

Meth Lab

Noxious fumes 유해증기 / 가스 Phosphine gas (PH3 , colorless, flammable, toxic gas , highly unpleasant odor like rotting fish) 고기썩는냄새

Anhydrous ammonia 무수 암모니아 Methylamine gas 메틸 아민 가스 Solvents (acetone, chloroform, ether, etc.) 용매 Iodine vapors 요오드 안개 / 가스 / 증기 White phosphorus Hydrogen chloride gas 염산 가스 Hydrogen iodide Methamphetamine vapors 필로폰 가스 Lithium/Sodium gases

Rolling Meth Lab – Moving Lab for illegal Meth production 움직이는 실험실 transportation hazard – flammable, explosive 가연성 , 폭발성 toxic effects, dangerous remnants – poisonous residue contamination 오염 움직이며 환경오염 ( 독성 ) 물질 남김 , 차량 내 합성

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Impurity Profiling 마약류 불순물 프로파일링을 설명하시오

Impurity Profile 불순물 프로 파일링

- the description( 기술 ), characterization( 특징설명 ) and quantitation ( 정량 )

of the identified( 확인 ) and unidentified impurities( 미확인 불순물 ) present

in new drug substances

약물 중에 있는 확인 , 미확인 불순 물에 대한 설명 ( 기술 ), 확인 , 정량 --- 왜 ???

100% of something ? – Possible ? 약물은 매우 순수 - 순도 높아야 함 – 인간 섭취

Impurity: any substance coexisting with the original drug, such as starting

material or intermediates or that is formed, due to any side reactions

불순물 - 목적하는 주 약물과 동시에 존재하는 미 반응 전구물질 ,

반응 분해물 , 반응 중간체 등

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Impurity Profiling 마약류 불순물 프로파일링을 설명하시오

3 types of impurity 존재하는 3 가지 불순물

1) Related to the product and coming from the chemical or from

the biosynthetic route itself 최종산물에 관련 - 전구체 , 다른화합물 , 화학공정

2) Formed due to spontaneous decomposition of the drug during the storage

or on exposure to extreme conditions 보관중 분해물 , 극심환경 노출 등

3) The precursors which may be present in the final product as impurities 전구체

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Impurity Profiling 마약류에 존재 할수있는 불순물에 대해 설명하시오

Impurity Profile 치료약 - 어떻게 , 왜 ? 1) Alter the reaction condition 반응조건변경 허용치 이내 2) Reduce the quantity of impurity to an acceptable level 불순물감소 3) To obtain a pure substance with less toxicity and safety in drug therapy 순수약물 취득 , 낮은독성 , 안전성 위해

Classification of impurities 불순물 분류A)Organic Impurities – process related, storage related 유기불순물 starting material, by-products, intermediates, degradation products reagents, ligands, and catalysts 제조과정 / 저장관련 , 부산물 , 중간체 , 분해산물B)Inorganic Impurities 무기불순물 reagents, ligands, catalysts, heavy metals or other residual metals, inorganic salts, filter aids, charcoal etc. 시약 , 리간드 , 촉매 , 중금속 , 금속 , 염C) Residual Solvents 잔존용매 organic, inorganic liquids during the manufacturing process - generally of known toxicity – can be easily controlled 제조공정사용 유기 , 무기용매 , 알려진 독성 , 조절가능

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Impurity Profiling 검출한계와 중요성을 설명하시오

Impurity Profile 불순물 일람표 / 도표 / 분석표 모르는 불순물 General acceptance of < 0.1% for any unspecified impurity 0.1% 이하 허용 For > 0.1% impurity – identified, quantified, synthesized to prove provide the final evidence -----------commercial drugs 상용약물 상품화 약물 , 순도의 최종 증거로사용 , 허용치 이상 – 확인 필요 0.1% 이상 - 확인필요 - 무엇인가 , 얼마나Detection of the impurities 불순물 동정법 / 검출 - TLC, HPLC, GC etc. - Procurement of standard impurity samples 표준불순물 입수 / 필요 last intermediate of the synthesis 최종 전 단계의 중간체 products of predictable side reaction 예측 가능한 부가반응물 degradation products if any etc. 최종산물의 분해산물

LOD (Limit of detection) 검출한계 - 일반 , 극미량 - 특히 불순물 the lowest concentration/amount of analyte in a sample that the method can detect, depends on the procedure of analysis & the type of instrument 어느 방법 ( 분석기구 , 분석방법 , 과정 등 ) 으로 검출 할 수 있는 최소농도 / 분석물의 양

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Drug Characterization / Impurity Profiling

Drug Characterization Studies 약물 특징 / 동정 ( 확인 ) 연구 - provide useful information for drug law enforcement authorities

마약류조사관에게 좋은 정보 제공 - The process of determining the exact molecular structure

of an organic compound 유기물 정확한 분자구조 결정과정

- The process of determining the major features of a drug sample( 약물시료 )

both its physical and chemical characteristics including the presence

and nature of cutting agents, the quantification of significant sample

components( 시료구성요소 ) and so on.

마약류시료의 물리 - 화학특징 , 희석제종류와 양 등

시료 중 주요 / 중요 성분 – 다른 것 존재 , 성질 동정 필요

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Impurity Profiling 마약류 불순물 프로 파일링 -Involves several analyses that are designed to produce 특정분석 과정포함 a detailed picture (profile) of a drug sample 불법약물시료 - 프로파일 in the form of chromatographic data 크로마토그래픽 데이터 the resulting chemical profiles – “signatures”, “impurity profiles”

- additional analyses-target the minor (trace) components in the sample

Ultimate goal – obtain profiles of the major & minor components in formats

that allow us to use data as a comparative tool for the purpose

of locating other samples having similar profiles. 비교분석 최종목표 - 전체윤곽 ( 일람표 ) 을 확인 – 주 / 부 구성성분 – 비교분석 다른 시료와 비교 – 유사 프로파일 가진 시료와

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Drug Characterization / Impurity Profiling 마약류 불순물 profiling 에 대해 설명하시오

Chemical links between samples can be established 화학적 관련성 - 연관성 마약 시료간의 관련성 Material from different seizures can be classified into groups of related samples specific links between suppliers and users 공급자 / 사용자 연관 drug distribution patterns/networks 약물 분배양상 geographic origin of drug samples 제조처

--- Forensic Chemist 법화학자 peculiarities of different drug types 서로 다른 약물의 특징들을 찾음 the implications of the presence or absence of different types of impurities - manufacturing impurities and cutting agents 조제 , 합성중 불순물 - 희석제들 다른 양상 / 패턴--- Close cooperation betw. Lab and law enforcement personnel essential to maximize the operational value 실험실 - 수사관 긴밀한 공조가 필수 - 최상의 결과

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Drug Characterization / Impurity Profiling ….continued

Plant-based: heroin, cocaine, cannabis etc. 식물기반약물Synthetic: various amphetamines 합성기반 one or more of 3 key components 1) natural components: present in raw material 자연산물 (ex. coca leaf, opium) co-extracted during drug production-not completely removed from the final product 2) by-products – generated during drug manufacturing 부산물 related to the method of manufacture 3) cutting agents: added at any point in the distribution 희석제 chain after manufacturing

Chemical Analysis of drug samples – major, minor, trace components 주 , 부 , 미세 Impurity Profiles – a “characteristic chemical signature” 산물 natural components, by-products, cutting agents can provide a complete “history” of the sample may play a key role in characterizing samples

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Drug Characterization Studies 약물특성 연구 - often require evidence to link drug dealers and users 판매자 , 사용자 연결 - want information on local distribution networks 증거 요구 asked to determine whether samples of seized drugs are related ? 압수 약물간의 관계 결정For evidence – prosecution purposes 증거 , 고소목적 For intelligence purposes – information 정보 locally, nationally, internationally 지역적 , 국가적 , 세계적

Generate general infos. for health authorities 범건강관련 부처 정보제공 - identification of unusual new drugs or drug combinations 신마약류 - unexpected health consequences – early warning system 경고 - improved understanding of drug abuse trends 남용경향 이해 일반적인 약물남용 경향등 이해

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Operational Value 실제 조작상의 가치 2 종이상 시료 1) Establish specific links between two or more samples 특별관련성 2) Establishing drug distribution patterns 약물 분배 / 판매 의 패턴 3) Identifying the source of drug samples 약물샘플의 소스확인 4) Monitoring methods used for clandestine drug manufacture 비밀합성방법 감시

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Physical & Chemical Examination by forensic chemist 법화학자의 물리화학실험

Type of sample – tablets, capsules, powders, liquids 여러형태 “natural” materials – opium, cannabis products

Visual inspection 육안검사 color, texture, general appearance - are they connected ? their packaging (materials, way of packaging, fingerprint etc.) characteristic marks 특징적 마크 색상 , 질감 ( 촉감 ), 일반 외형Chemical examination – analysis – impurity profiles 화학적 검사 comparing & grouping different seizures 압류 , 압수물 비교 , 조합

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Factors 실험 / 확인에 영향을 미치는 요인

Natural & semi-synthetic drugs – cocaine, heroin, cannabis products 천연 / 반합성By Geographic origin of the raw materials (opium or morphine base, coca leaf) General procedures used for the extraction, conversion, purification - contribute impurities of final product 원산지 – 천연물 원료 제조 / 처리 과정 ---- 최종물의 불순물에 영향Synthetic drugs – Ams 합성물 - 암페타민류 Quality of the starting materials used 전구물의 질 - 무엇이든 100% 는 없다 the route of synthesis 반응경로 the reaction conditions 반응조건 the extent of purification of the final product(s) 최종물질 순수분리정도 --- overall the skills of the clandestine chemist 비밀실험실 화학자의 전반적 기술

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Batch - A quantity of anything produced at one operation 한번에 만든 분량 ( 것 )

but production conditions – can’t be the same 만든조건 - 동일불가 variation will occur 변화 , 변동 , 편차 가 일어날수있다

Inter-batch variation – usually bigger than intra 배치간의 변동 / 차이 내보다 크다Intra-batch variation 배치 내 변동 / 차이 – 적다 , 그러나 존재

Possible only if sufficient infos. generated by analytical method 분석법으로 충분한 정보를 확보한 경우 유용

Particularly high variation for natural, semi-synthetic drugs 천연 , 반합성 -큰 변동 - crude Lab conditions associated with their production 조악한 실험환경 - the process of production 생산 과정-Exam. of physical characteristics, materials used for packaging 물리적특성 - can provide infos. to link the samples 특정포장재료 시료간의 연결고리에 대한 정보 제공가능

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Batch variation in synthetic drugs 합성약물의 뱃치상 다른점 - inter, intra-batches – relatively small - little difference in impurity content across a singe batch of a drug -More closely controlled conditions with synthetic drugs 조절된 조건 / 환경 than Natural, Semi-synthetic drugs 사용 합성 May be linked by their impurity profile 합성불법 약물이 반 합성약물 보다 변동이 적다

The presence or absence of specific impurities (marker) 특정불순물의 존재 determining synthetic route employed 사용합성경로 결정 starting materials (precursors) used 사용된 전구 , 출발물질 Also solvent analysis 또한 용매분석

---depends on the method of synthesis 합성법---the proportions---source and purity of starting materials 시작물질의 순도 , 근원---the reaction conditions 반응조건 ---the purification procedures 순수분리과정 28


Drug Supply – long & complex 마약류공급 - 길고 ,복잡 producer (source) trafficker distributor supplier user cutting agents (diluents, adulterants) may be added at each stage - impurities profile – more complex 희석제 , 불순물 - 어느부분에서 혼입 ?

던져야 할 질문들 But in practice ---- chain of supply (same?), distribution network 하지만 실제 상황에서 – 쉬운 판단이 아님 보급 , 분배 망 /네트워크Indistinguishable chemical profiles of samples - samples are linked by a common history 화학프로파일 - 동일 - 공통의 보급역사 / 동일 보급로 ?Samples from different levels in the distribution chain - different cutting agents (?)

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Strength of evidence 증거의 힘 / 결정력 - A measure for the validity/quality of the result, the conclusions drawn from them 결과의 유용성 / 질 에서 도출한 결론의 척도 - The presence of unusual cutting agents 흔치 않은 희석제의 존재 - Other investigative approaches (ex. Packaging materials) 다른 수사접근방법 – 포장사용 물질

“Ageing” 노화 , 숙성 약물의 주성분 , 불순물의 시간 경과 에 따른 분해 due to decomposition of main drug and/or accompanying impurities 분해과정 - exposure to light, heat, air etc. 빛 ,열 , 공기 노출 - exposed to different environments during the supply chain 공급 과정중 - 다른환경접촉 - certain aggressive cutting agents (ex. Ascorbic acid) 희석제가 공격적 ? 화학 , 물리적으로 희석제 , 부형제의 성분과의 공격적 반응

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Internet & Drugs 인터넷통한 불법약물 구입

Web sites based Drug selling 인터넷 약물판매 - outside USA, SK etc., serious public health risk 국민보건위험요소 - causes a big problem for law enforcement officials 사법당국에 큰 문제 - without prescription, by mail 우편판매 처방없이 - opiate, barbiturates, benzodiazepines, hallucinogens, other stimulants etc.

Needs only a shipping address & a payment method 주소와 지불 방법만이 필요Claims that “less than a one % chance of package being seized” 1% 이하만이 검열에 걸린다고 주장Uncontrolled access – increase in addition & overdose deaths especially young people 무작위 접근가능 – 위험증가

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2013 fall 9th class illegal produc약물남용, 사이버마약

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Transcript of 2013 fall 9th class illegal produc약물남용, 사이버마약