Aula 1 21 de Fevereiro de 2018

Aula 1 –21 de Fevereiro de 2018

Helena Gaspar

[email protected] Gab 8.5.49, Lab 8.5.55

Programação

Aula Semana Docente

1 21 Fevereiro Helena Gaspar, FCUL 2 28 Fevereiro Helena Gaspar, FCUL

3 7 Março Ana Assis, Diretora do Sector de Fisico-Química,

Labolatório de Polícia Científica (LPC) da Polícia Judiciária (PJ) 4 14 Março Maria João Caldeira, Diretora do Sector de Toxicologia do

Labolatório de Polícia Científica (LPC) da Polícia Judiciária (PJ) 5 21 Março Júlio Nunes, Diretor da

Autoridade Antidopagem de Portugal (Adop) 6 4 Abril Ricardo B. Silva, FCUL

7 11 Abril Ricardo B. Silva, FCUL 8 18 Abril Ricardo B. Silva, FCUL

9 2 Maio Suzana Fonseca e Mário Barroso

Serviço de Química e toxicologia Forenses do INMCF

10 9 Maio Vistia ao Laboratórios do Serviço de Química e toxicologia Forenses do INMCF 11 16 Maio Eugénia Galhardo, UBI

12 23 Maio Visita ao Labolatório de Polícia Científica (LPC) da Polícia Judiciária (PJ) 13 30 Maio Helena Gaspar, FCUL

Avaliação

• Exame final (60%)

• Avaliação durante as aulas teórico-práticas (2O %)

Resposta a questões nas aulas (10 min/TP)

• Análise de um caso real,incluindo apresentação oral e discussão (2O %)

(Identificação de catinonas/canabinoides)

Para fazer o exame final será necessário ter nas outras componentes a nota mínima de 10 valores

Para ter aprovação na disciplina a nota do exame tem

ser superior a 9,5 valores.

Forensic Sciences

Use scientific evidence for legal purpose

Forensic Chemistry

Forensic Chemists

Application of chemistry to collect,

preserve, and analyse scientific evidence for legal purpose

Forensic

from Latin forẽnsis meaning forum and also relate with foris, “outside” – a “public place outside” where the Roman debated,

performed and held judicial proceedings

https://webapps.worldbank.org/sites/WBAT/Pages/default.aspx https://mundoalice.wordpress.com/2011/02/12/tribunal/tribunal-300/

http://www.fullscreen360.com/roman-forum

Both sicentis examing the same piece of evidence but arrive at different conclusion!

Methodology must be holistic!

1

2

5 4

6 3

French Criminalist

http://www.slideshare.net/leahmorgan/forensics-ch-1-notes

Locard Exchange Principle

”Toute action de l’homme, et a fortiori, l’action violente qu’est un crime, ne peut pas se dérouler sans laisser quelque marque”,

La police et les méthodes scientifiques (1934)

“ Every contact leaves a trace ” Edmon Locard, 1877-1966 Pionieer of Forensic Science

1910- Fisrt world forensic Science Lab in France

http://www.sherlockian-sherlock.com/ edmond-locard-sherlock-holmes-of-france.php http://www.forensichandbook.com/dr-edmond-locard/

Ninhydrin react with skin amino acids to produce a purple colour

FINGERPRINT

http://classroom.sdmesa.edu/eschmid/Lab4-Biol210.htm

Collecting Evidence using Chemistry

heat

+ RCOH+ CO₂

Ninhydrin

purple-coloured product

BLOOD STAINS

http://chemincrime.weebly.com/luminol-test.html

http://www.bluestar-forensic.com/gb/bluestar-chemistry.php

Synthesis of luminol - 1853

Luminescência with blood -1928 by Albrech Forensin tool- 1937 bySpecht

Collecting Evidence using Chemistry

The Iron from the haemoglobin

catalyse the formation of luminescent

“Solely the dose determines that a thing is not a poison”

Paracelsus, 1493-1541

“A dose distingue o veneno do remédio”

.

Paracelsus, pseudonym of Philippus Theophrastus Aureolus Bombastus von Hohenheim, Swiss physician and an alchemist

• The “father” of chemistry and the reformer of Materia Medica

• The “Luther” of Medicine

• The “godfather” of modern chemotherapy

• The founder of medicinal chemistry

• The founder of modern toxicology

Joseph F. Borzelleca , Paracelsus: Herald of Modern Toxicology,Toxicol Sci (2000) 53 (1): 2-4

http://www.kvarkadabra.net/en/2016/06/paracelsus-martin-luther-of-medicine/

“Somente a dose distingue o veneno do remédio”

6 litros de água

118 cafés

Dose Letal

DL-50 (mg/Kg)

Quantidade de substância

necessária para matar

metade da população

de teste

Mathieu Orfila, Catalão 1787-1853

Fundador da Toxicologia Experimental

& Medicina forense

https://archive.org/details/traitdespoison01orfi https://www.iesfelanitx.cat/departaments/fisica-quimica/orfila/obra.htm

1814 –Traité des Poisons tires des régnes mineral vegetal et animal

Estudo dos efeitos adversos das substâncias químicas em seres vivos Meios de diagnostico para detetar estas substânias

Formas de tratamento

Autopsia e análise toxicológica como evidência de intoxicação

para fins legais

Envenenamento por Arsénio (Metal)

http://mundoquimico.com.br/metodo-para-deteccao-de-envenenamento-por-arsenico/

As (metal cinzento) → As

O

(pó branco) Sem sabor

Sem cheiro

Deteção de envenenamento por Arsénio

James Marsh, 1794-1846 Químico Escocês

1832 - Marsh usou um teste tradicional para detetar arsénio na vitima George Bodle (teste positivo/não culpado)

Forensic Chemistry, David E. Newton, 2007 https://estudogeral.sib.uc.pt/handle/10316/12322

As

O

+ H

S → As

S

Deteção de envenenamento por Arsénio James Marsh, 1794-1846

Químico Escocês

1836 – O teste de Marsh foi a primeira análise confiável que poderia demonstrar cientificamente que o arsênico estava presente no corpo da vítima.

Forensic Chemistry, David E. Newton, 2007

As

O

+ 6Zn + 6H

---> 2As

+ 6Zn

+ 3H

O As

+ 3H

---> AsH

2AsH

(calor) ---> 2As + 3H

https://estudogeral.sib.uc.pt/handle/10316/12322

Deteção de envenenamento por Arsénio

1840 - Orfila detectou arsênico no tecido da vítima usando o teste Marsh:

Marie Lafarge foi a primeira pessoa condenada com base em evidência toxicológica

Forensic Chemistry, David E. Newton, 2007

https://estudogeral.sib.uc.pt/handle/10316/12322

teste Marsh

Julgamento Marie Lafarge

Jean Servais Stas 1813 -1891

Belgian Chemist

1828 - Nicotine, vegetal alkaloid isolated from Nicotiana tabacum

1851 - Stas was the first to detect vegetable poisons in victim´s organs for legal purpose

Detection of vegetable poison in the human body

Análise Química Forense em Portugal

Chimica Legal (Lab Coimbra, Porto e Lisboa) iniciado em 1899

Antonio Joaquim Ferreira Silva (1853-1923), Professor de Química e Diretor do laboratório da Academia Politécnica e do Laboratório Chimico Municipal do Porto

• Descoberta de reações caracteristicas da cocaina e eserina

• Desenvolvimento de um reagentes usado na deteção da Morfina e Codeína (Reagente de Lafon e Ferreira da Silva)

M. Fátima Pinheiro, Ciências Forenses ao Serviço da Justiça, PACTOR 2013

Antonio da Costa Simões (1819-1903),Professor da Faculdade de Medicina da U. de Coimbra Deteção de substâncias tóxicas em suspeitos envenenamentos no Laboratório Chimico da Faculdade de Filosofiaque publicou na revista “O Instituto” em 1855

“analyse d’uns fragmentos de substância branca achanos no estomago:analyse do mesmo estômago e dum liquido e mais subtãncias que se tinham encontrado nesta víscera, mandados de Villa Cova, julgado de Fráguas” in A. J. Leonardo et al, Antonio da Costa Simões e a génese da química forenses em Portugal

Papaver somniferum

Natural Products are a traditional source of medicines and recreational drugs

•

First Natural Product isolated in 1806

•

Opium used since 3400 a.C

•

Opioid - analgesic alkaloid

•

Medicine

Morphine

Toxicologia Forense, R. J. Dinis-Oliveira, F. Dias Carvalho, M. L. Bastos, 2015, Pactor

Erythroxylon coca

Natural Products are a traditional source of medicines and recreational drugs

Cocaine

First isolated in 1860 by Coca used since 2500 a.C Stimulant alkaloid

1863- French Tonic (0.2mg/mL)

http://blog.medfriendly.com/2012/07/medical-history-of-coca-cola-you-never.html http://thenonist.com/index.php/thenonist/permalink/vin_mariani/

1886–First Coca-Cola recipe Crack –free base

Morphine

Heroin first semi-synthetic drug

Felix Hoffman, from Bayer synthesised Heroin in 1897 Heroin

Charles R.A. Wrigh In 1874 made Heroin from morphine

Albert Hofamann 1902-2008

“Lyserg-säure-diäthylamid” from German

“Dietilamina do ácido lisérgico”

LSD a semi-synthetic hallucinogenic drug

LSD

First synthesised LSD-25 in 1938

Ergotamine

From fungus Ergot

60's hippie movement

Amphetamines, Stimulant drugs used during World War II

First use in 1920s as a descongestant and also for obesity and depression

• Synthetised from ephedrine in 1893 by Akira Ogata

• The German pharmaceutic Temmler produce Previtin Methamphetamine

Amphetamine

• Discovered in 1887 for Romanian chemist

• 1933 marketed in USA as Benzedrine

Temmler Pervitin, used during World II

Popular in 80's and 90's

Ecstasy, the RAVE Party Drug

3,4-Methylenedioxymethamphetamine

MDMA

• 1912 Synthesised by Anton Köllisch from Merck

• Never marketed as medicine

• Amphetamine

• Stimulant in Central nervous system (CNS)

• Addictive drug

• 1977 banned in UK

• 1993 banned in Portugal

EU Drug Markets Report: In-Depth Analysis, EMCDDA–Europol Joint publications 2016

1991 PiHKAL

Phenethylamines I Have Known and Loved 179 derivatives

Synthesis and personal experiences with psychoactive drugs!

Alexander Theodore

"Sasha" Shulgin (1925 -2014) American Chemist

1997 TiHKAL

Tryptamines I Have Known and Loved 55 derivatives

Ann Shulgin (1931)

https://twitter.com/drashulgin

https://www.erowid.org/library/books_online/pihkal/pihkal024.shtml https://erowid.org/library/books_online/tihkal/tihkal.shtml

Smartshops PT

Sobre o fundo verde fluorescente da montra é exibido o principal cartão-de-visita do estabelecimento comercial:

"A tua loja de drogas legais." É desta forma que a Cogumelo Mágico, a primeira smart shop a abrir fora da Holanda na Europa, se apresenta à clientela que vai circulando pelo Centro Comercial Oita, em Aveiro.

http://www.publico.pt/local/noticia/primeira-loja-de-drogas-legais-aberta-em-aveiro-1285210

Público 09/02/2007

2007/2013 – Open 63 Smartshops in Portugal

2007 – Appears in Portugal the first smartshop in Europe outside Netherlans!

Smartshops Products – Legal Drugs

N

P

HERBAL INCENSE

P

S

C

P

E

Chemical Compositions? Nobody knew!

Legal Drugs  Safe

Smartshops PT

Madeira tenta reduzir oferta das smatshops

Publicado a 04 DEZ 12 às 00:18 TSF Rádio Notícias

A entrada em vigor desta lei fez diminuir o número médio de casos no hospital de cinco para um e de 20 para quatro na Casa de Saúde S. João de Deus.

Este responsável adiantou que estas drogas foram responsáveis por 190 internamentos na Casa de Saúde,

«alguns dos quais com danos irreversíveis, nomeadamente com o aparecimento de esquizofrenias e outras psicoses e perturbações psiquiátricas».

http://www.tsf.pt/PaginaInicial/Vida/Interior.aspx?content_id=2925276

NPS over the net and dark net

Data de pesquisa

12-02-2017

Venda NSP na internet

Data de pesquisa

17-02-2018

http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)61462-6.pdf

Relative Risks of Drugs

Nutt, David J, et al., “Drug Harms in the UK: A MulticriteriaDecision Analysis.”The Lancet376, no. 9752 (2010): 1558-65.

DRUGS CONTROL

• 1909 – The “national” Chinese heroin problem lead to the creation of The Shanghai Opium Commission

• 1912 – Born the first mechanism for the international legislation of drugs The Hague Opium Convention

• 1961 – United Nations (+ 180 countries) created The Single Convention on Narcotic Drugs

(It seeks to limit the manufacture, possession and use of drugs to science and medicine)

• 1971 - United Nations created in response to the widening rang of abuse drugs The Convention on Psychotropic Substances

A psychotropic substance is defined as “any substance, natural or synthetic, or any natural material in Schedule I, II, III or IV” of the convention

• 1988 – United Nations created

The Convention Against the Illicit Traffic in narcotic Drugs and Psychotropic

Substances

Drugs Control - Actual Scheldules (last update in 2016)

https://www.unodc.org/unodc/en/commissions/CND/conventions.html

Heroin Synthesis

LSD

1988 UN Convention Against the Illicit Traffic in narcotic Drugs and Psychotropic Substances

https://treaties.un.org/doc/Publication/UNTS/Volume%201582/volume-1582-I-27627-English.pdf

Original Tables

Methamphetamine

Most of abuse drugs are sold as hydrochloric salts

https://www.unodc.org/unodc/en/commissions/CND/conventions.html

A CTUAL T ABLES

Synthesis of hidrochloric salts

Solvents

and chemicals Precursors and

pre-precursors

https://www.unodc.org/documents/southeastasiaandpacific/2014/

05/gsda/clean/2014_Global_Synthetic_Drugs_Assessment_CH9.pdf

https://www.incb.org/documents/PRECURSORS/TECHNICAL_REPORTS/2014/2014-PreAR_E.pdf

1988 UN Convention – Precursors Evolutions

Beginning of Pre-Pre-Precursors ERA

3-oxo-2-phenylbutanamide APAAN

P2P

“The control of APAAN, however, has prompted further chemical innovations in the precursor market. The finding of 3-oxo-2-phenylbutanamide, a substance that can be readily converted to APAAN, in a Dutch amphetamine laboratory in 2013, indicates that criminal groups have managed to circumvent controls on APAAN”

http://www.emcdda.europa.eu/start/2016/drug-markets

EU Drug Markets Report: In-Depth Analysis, EMCDDA–Europol Joint publications 2016

Methamphetamine amphetamine

Precursor Pre-Precursor Pre-Pre-Precursor

• The United Nations Office on Drugs and Crime (UNODOC, https://www.unodc.org/)

• The European Network of Forensic Science Institutes (ENFSI; http://enfsi.eu/)

• The Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG; http://www.SWGDRUG.org), USA

I NSTITUTIONS THAT CAN DEVELOP STANDARDS AND

GUIDELINES FOR THE ANALYSIS OF DRUGS

“A ‘new psychoactive substance’ means a substance in pure form or preparation that has not been scheduled under the 1961 United Nations Convention on Narcotic Drugs and the 1971 United Nation Convention on Psychotropic Substances

and that may pose a threat to public health”

NPS New Psychoactive Substances

Council of the European Union,“CouncilDecision 2005/387/JHA of 10th May 2005”

• New - new in the drugs market ≠ a new molecule

• Widespread – “smartshops” and Internet

• Several associated health problems and deaths

• More than 628 NPS were reported in the EU

• Natural Products or Designer Drugs

NPS New Psychoactive Substances

NPS, a legal alternative to illicit drugs

JWH-018

MDPV Methylone

Mephedrone

1971 United Nation Convention on Psychotropic Substances Synthetic cathinones

Synthetic Cannabinoids

C

C

,

(

)

EMCDDA (http://www.emcdda.europa.eu/about)

The European Monitoring Centre for Drugs and Drug Addiction established in Lisbon in 1995

http://www.emcdda.europa.eu/themes/new-drugs/early-warning

1993 -Monitoring the drug phenomenon across Europe

http://www.emcdda.europa.eu/publications/brochures/rtxfaq

EWS Early Warning System in EU

appears in 1997 due to NPS phenomenon

Reitox

Réseau Européend´Information sur le Drogues et les Toxicomanies 30 countries (28 EU member states + Noruega +Turquia)

Each mender have a reitox national focal point

Portugal

http://www.emcdda.europa.eu/themes/new-drugs/early-warning

EMCDDA Information about a new NSP

Focal point of each country's REITOX network

Rapid information exchange

EWS Early Warning System in EU

http://www.emcdda.europa.eu/themes/new-drugs/early-warning

EWS Early Warning System in EU

Risk Assessment of 21 NSP

The health and social risks, caused by the use of, the manufacture of, and traffic in a new psychoactive substance, the involvement of organised crime and possible consequences of control measures.

Type of warnings

• Identifications of a Novel NSP

• Large drug seizures

• Public health alerts

These 6 substances were associated to:

+ 200 deaths

+ 700 non fatal intoxications

>450 NSP

Identifications made by analytical techniques

MDPV 4,4´- DMAR

AH-7921 MT-45 Opioids

Arylamines 25I-NBOMe

Phenilethylamines

Risk Assessment Others

Cathinones

Methoxetamine

EWS - Example 2014

http://www.emcdda.europa.eu/html.cfm/index16776EN.html

1971 C

P

S

Schedule I 25B-NBOMe (2C-B-NBOMe)

25C-NBOMe (2C-C-NBOMe)

Schedule II Mephedrone

3,4-Methylenedioxypyrovalerone (MDPV)

Methylone (beta-keto-MDMA)

N-benzylpiperazine (BZP) JWH-018 e AM-2201

1961 C

N

D

Schedule I

2015- Ten NPS Scheduled in UN convention

Commision on Narcotic drugs

58th session, 13 March 2015

Desafios de NSP

Já foram reportadas ao obeservatório mais 628 NSP !

628

EMCDDA–Europol 2016 Annual Report on the implementation of Council Decision 2005/387/JHA, EMCDDA, Europol, Lisbon, July 2017

Helena Gaspar Análise Química Forense 21 de Fevereiro de 2018

Desafios de NSP

Observatório Europeu da Droga e da Toxicodependência (2017), Relatório Europeu sobre Drogas 2017: Tendências e evoluções, Serviço das Publicações da União Europeia, Luxemburgo.

Famílias +NSP

Catinonas Sintéticas (118) Canabinóides Sintéticos (169)

70% detetadas pela 1º vez nos últimos 5 anos !

Já foram reportadas mais 628 NSP !

Mimetic cannabinoid

JWH-018

Classic

THC

CP47,497

Synthetic Cannabinoids

JWH-018

JWH-122 MAM2201 JWH-210 JWH-250

AKB48 AM694 AM1248 UR-144 AM694-Cl derivative

Synthetic Cannabinoids Evolution

http://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids

Synthetic Cannabinoids

16 –tails

10 –Primary Structure 4 – link

17 –Secondary Structure

Total 169 NS

tail

link

2

9 11

23

30 29 30

24

0 5 10 15 20 25 30 35

2008 2009 2010 2011 2012 2013 2014 2015

16 x 10 X 4 x 3 x 17 =

10 880

• Normaly found in herbal insensces

• Synthetic Compounds sprayed on herbal matrices

• Not for human consumption

• Mostly contain Synthetic Cannabinoids

Synthetic Cannabinoids

tail

link

SGT-25

CUMIL-5F-PINACA

http://www.safecoalition.org/2014-07-17-e-cigarettes-and-synthetic-drugs-part-ii

'Techy appeal"

SGT-25

NSP 2014

PATENTE WO 2014/167530 A1

Synthetic Cannabinoids Evolution

Synthetic cathinones Khat, plant Catha edulis

cathine

(β-keto-amphetamines)

Cathinone amphetamine

http://www.emcdda.europa.eu/topics/pods/synthetic-cathinones-injection#ref5Online http://www.emcdda.europa.eu/publications/drug-profiles/synthetic-cathinones

Synthetic Cathinones

Methylone 2005 Netherlands MDMA - Ectasy

3,4-methylenedioxy-N-methcathinone 3,4-methylenedioxy-N-methamphetamina

Mephedrona

Synthetic Cathinones

Mephedrone - New drug old compound

2003 – drug market 2007 – net market 2008 – Ilegal Israel 2010 – Ilegal Europe

2015 – UN Convention control

"Sur un homologue de l'éphédrine"

Bulletin de la Societé Chimique de France 45: 284

Mephedrona

4-metyl-N-methilcatinona

http://www.emcdda.europa.eu/publications/drug-profiles/synthetic-cathinones

Synthetic Cathinones

Total 118 NS

2005-2013 50 NS 2014 31 NS

2015 26 NS

Possible strutures

15 x 2 X 6 x 3 x 6 = 3240

NPS Challenge

Faster Identification of NPS without standards The huge rate of emerging NPS (almost 1/2 per week)

Why?

NPS Challenge - Faster identification

For human health

Identification of NPS is crucial for toxicological evaluation

For a Forensic Chemist Unequivocal identification of NPS is imperative

for a correct law application

To prevent the risks associated

to the consumption of NPS To an effective control of NSP

Control of Drugs in Portugal

Decreto-Lei 54/2013, 17

May

Forbids the production and commercialisation of 159NPS

Need for adequate analytical methodologies and standards Decreto-Lei 15/1993, 22th January

Criminalizes the traffic of narcotics and psychotropic substances following:

• National decision

• WHO recommendation

• Commission on Narcotic Drugs decision

• EU Council Decision

Classical drugs all procedures are well established

http://www.pgdlisboa.pt/leis/lei_mostra_articulado.php?nid=181&tabela=lei_velhas&nversao=1&so_miolo=

• Feniletilaminas e derivados (48)

• Piperazina e derivados (8)

• Derivados da catinona (34)

• Canabinoides sintéticos (46)

• Derivados/analogos da cocaina (4)

• Plantas e respetivos constituintes ativos (6)

• Outors (13)

Lista 159 NPS 2013

EMCDDA 628 NPS 2016 Catinonas 118

Canabinóides sintéticos 169

http://www.sicad.pt/BK/Institucional/Legislacao/Lists/SICAD_LEGISLACAO/Attachments/850/Portaria_154_2013.pdf

Protocol NPS 2014

The role of FCUL

• To help in the identification of NPS for court cases

• To supply NPS for the creation of an “in house” GC-MS library at LPC

• To supply NPS for toxicity evaluation at FFUP/FCUL

Forensic Chemist