FACT SHEET Pcpp

FACT SHEET

pCPP

September 2016

For more information, please contact: Dr. P. Blanckaert Coordinator Belgian Early Warning System Drugs Scientific Institute of Public Health National Focal Point on Drugs Jyliette Wytsmanstraat 14 B-1050 Brussels, Belgium Tel : 02/642 5408 [email protected]

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A. General information

Recent collected sample in Belgium Substance: pCPP mixture with amphetamines Date of Collection: August 2016 Date of analysis: September 2016 Color: Pink Region: Brussels Diameter: 8mm Thickness: 5mm Tablet weight: 230 mg

Created September 2016

Updated /

Type Psychotropic Substances

Group Piperazine Derivates

Name p-Chlorophenylpiperazine (pCPP)

Nature of substance pCPP is a piperazine-derived designer drug, which has been reported for the first time in the Reitox Early warning system through a Reporting Form in November 2006 by France.

Systematic chemical name 1-(4-chlorophenyl)piperazine

Other names 1-(4-chlorophenyl)piperazine is the systematic chemical name but the substance is better known by one of its codenames pCPP (where ‘p’ stands for para, signifying the fourth position of the chlorine atom on the phenyl ring, and ‘CPP’ stands for chlorophenylpiperazine), 4CPP or 4Cl-PP. Depending on the position of the chlorine atom, other possible CPP isomers are 1-(3-chlorophenyl)piperazine (for meta- CPP) and 1-(2-chlorophenyl)piperazine, (codenames oCPP (for ortho-CPP), 2CPP or 2Cl-PP). As use of codenames could be confusing, they should be used only for initial orientation.

B. Alerts

Alerts The Belgian Early Warning System Drugs (BEWSD) issued an alert in september 2016 concerning a tablet containing amphetamine and pCPP.

Reports to EMCDDA Latvia: In its EWS Report for the 1st half of 2009 the NFP reported 12 seizures totalizing 952 tablets and 2 seizures of 3.2532g powder.

Sweden: In its EWS Report for the 1st half of 2009 the NFP reported 1 seizure of 0,73g powder; 1 seizure of 5 capsules; 25 seizures of tablets, 249 units; 4 seizures of tablets, 497 units. (reported as mCPP or pCPP).

Switzerland: On 25 July 2009 an ecstasy tablet containing pCPP (36.24mg) and mCPP was reported in Switzerland for the first time.

Latvia: In its EWS Report for the 1st half of 2008 the NFP reported 5 seizures of 22 tablets.

Bulgaria: In March 2007 the NFP reported 1 seizure of 49.385 g white tablets with Rolls Royce logo seized in Asenovgrad in 2006. Tablets containing 5% MDMA.

Bulgaria: In March 2007 the NFP reported 1 seizure of 64 white tablets with "Crocodile" logo seized in Kardzhali in 2006.

Bulgaria: In March 2007 the NFP reported 1 seizure of 1 white tablet with Rolls Royce logo seized in Sofia in 2006. Tablet containing 6% MDMA.

Bulgaria: In March 2007 the NFP reported 1 seizure of 1 white tablet with Mitsubishi logo seized in Varna in 2006. Tablet containing 1% MDMA and caffeine.

Bulgaria: In March 2007 the NFP reported 1 seizure of 3,55 g white tablets with Mitsubishi logo seized in Varna in 2006. Tablets containing 27% MDMA.

Bulgaria: In March 2007 the NFP reported 1 seizure of 260 white tablets, "heart" logo, seized in Varna in 2006. Tablets containing 1% MDMA.

Bulgaria: In March 2007 the NFP reported 1 seizure of 3 white tablets, Mitsubishi logo seized in Sofia in 2006.

France: In November 2006 the NFP reported a collected sample of powder. It was collected in Lyon in September and was sniffed in a party.

C. Pictures

Recent collected sample in Belgium

D. Clinical information

Usage A number of piperazine derivatives have been reported as recreational drugs. Only limited investigations have been conducted on the proprerties of pCPP. The isomers, predominantly mCPP, have been used as surreptitious substitutes for MDMA. Scientific research has demonstrated pCPP to have serotonergic effects, likely acting as a non-selective serotonin receptor agonist and/or releasing agent.

Health risks headache, nausea, severe halucinations, drunkenness. following the recreational use of piperazine party drugs, users may experience periods of exertion, lack of sleep or dehydratation.

Other uses /

E. Legal status

Belgium: controlled as of 22 October 2006

F. Chemistry

Other chemical names and variants Para-chlorophenylpiperazine (see also code names)

Chemical Abstracts Service (CAS) registry number pCPP (CAS# 38212-33-8)

Molecular information The piperazine-derived designer drugs could be divided into: (a) benzylpiperazines – including 1-benzyl-piperazine (BZP); and 1-(3,4- methylenedioxybenzyl)piperazine (MDBP); and (b) phenylpiperazines – including (1-(4-methoxyphenyl)-piperazine (MeOPP); 1-(3- trifluoromethylphenyl)-piperazine (TFMPP); 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-chlorophenyl)piperazine (pCPP).

Molecular structure:

Molecular formula: C10H13ClN2 Molecular weight: 196.68

Identification and analytical profile See annex: "Analytical profiles of the piperazines", from the LTG (formerly known as the London Toxicology Group)

G. References

Analytical profiles of the piperazines

Over the past few months (Autumn 2006) members of LTG have become aware of an increasing number of piperazine compounds sold on websites as “herbal ecstasy”. They are often promoted as a legal alternative to MDMA, sometimes as a “harm minimisation” strategy. None of the compounds are licensed medicines or have been evaluated for their safety. The health consequences of the widespread availability are beginning to emerge with reports of hospitalisations and involvement in road accidents.

This monograph presents brief analytical profiles of the piperazine derivatives found in “illicit” tablets and capsules in the UK. Not all the compounds listed have been found in products but are presented because they are positional isomers of those that have. Isomers that are not resolved by GC/MS may be differentiated by HPLC with UV diode array detection because the UV absorption spectra vary.

Analytical standards of all the compounds are available commercially from Sigma Aldrich, the catalogue numbers are provided in the table. Some compounds are only available as free bases, for others the hydrochloride salts are also available.

Some immunoassays that target methylamfetamine also detect some of the piperazines. Dilutions of a 1mg/mL solution of the compounds in methanol were made in water for the evaluations of the immunoassay unit test devices. Thanks are due to Alan Freke of Dade Behring for donation of the Syva RapidTest d.a.u. devices. The compounds

NN 1-benzylpiperazine BZP A C H N mw 176 11 16 2, Sigma Aldrich 13815-25G-F

1-(4-fluorophenyl)piperazine B C10H13FN2, mw 180 pFPP NN F Sigma Aldrich 19133-7 1-(3-trifluoromethylphenyl) piperazine m-trifluoromethylphenylpiperazine NN C C11H13F3N2, mw 230 TFMPP 1-(α,α,α-trifluoro-m-tolyl)piperazine CF Sigma Aldrich T8948 (HCl) 3

1-(3-methylphenyl)piperazine NN D C11H16N2, mw 176 mMPP Sigma Aldrich R435376 (diHCl) CH 3 1-(4-methylphenyl)piperazine E C11H16N2, mw 176 pMPP NN CH3 Sigma Aldrich 71868-5G-F

1-(2-chlorophenyl)piperazine NN F C10H13ClN2, mw 196.5 oCPP Sigma Aldrich C67605 (HCl) Cl

1-(2-methoxyphenyl)piperazine NN G C11H16N2O, mw 192 oMeOPP Sigma Aldrich M22601-5G (HCl) CH O 3

1-(3-chlorophenyl)piperazine NN H C10H13ClN2, mw 196.5 mCPP Sigma Aldrich 125180-5G (HCl) Cl

1-(4-methoxyphenyl)piperazine NN OCH3 I C11H16N2O, mw 192 pMeOPP Sigma Aldrich 571415-1G (diHCl)

1-(4-chlorophenyl)piperazine J C10H13ClN2, mw 196.5 pCPP NN Cl Sigma Aldrich C68008

1,4-dibenzylpiperazine NN K C18H22N2, mw 266.4 DBZP Sigma Aldrich S383937-1EA (diHCl)

GC/MS

Samples were analysed on a Shimadzu QP2010 gas chromatograph mass spectrometer with an HP5MS column (30m x 0.25mm, 0.50µm).

Column oven temperature 80°C Injection temperature 225°C Injection mode Split Split ratio 10:1 Carrier gas Helium Flow rate 1.0 ml/min Pressure 9.5 psi Ion source temperature 200°C Interface temperature 250°C

Column oven temperature programme: Rate Final temperature Hold time - 80°C 4 minutes 40.00°C/min 290°C 10.75 minutes

Chromatogram:-

(x10,000,000) TIC (D),(E) I.S 8.898

I.S 10.068 1.00 (F),(G) 8.943

7.444 (B),(C)

0.75 9.325

8.554 (H),(I),(J) (A) 8.478 0.50

0.25

0.00 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0

Retention time ID Compound Name Abbreviations (mins.) I.S. Quinoline - 7.444 A Benzylpiperazine BZP 8.478 B 1-(4-fluorophenyl)piperazine pFPP 8.554 (front) C m-trifluoromethylphenylpiperazine TFMPP 8.554 (tail) D 1-(3-methylphenyl)piperazine mMPP 8.898 E 1-(4-methylphenyl)piperazine pMPP 8.898 F 1-(2-chlorophenyl)piperazine oCPP 8.943 (front) G 1-(2-methoxyphenyl)piperazine oMeOPP 8.943 (tail) H 1-(3-chlorophenyl)piperazine mCPP 9.325 (front) I 1-(4-methoxyphenyl)piperazine pMeOPP 9.325 J 1-(4-chlorophenyl)piperazine pCPP 9.325 I.S. Pyribenzamine (tripelenamine) - 10.068 K 1,4-dibenzylpiperazine DBZP 10.768 (not shown)

(A) BENZYLPIPERAZINE (BZP) 8.478mins

100.0 91.1 NN 75.0 134.1

50.0

25.0 56.1 176.1 42.1 85.1 120.1 0.0 161.2207.0 252.9281.0 326.9 50 100 150 200 250 300 350 400

(B) 1-(4-FLUOROPHENYL)PIPERAZINE (pFPP) 8.554mins

100.0 138.1 NN F

75.0

50.0

25.0 180.1 122.1 56.1 95.0 42.0 75.0 0.0 150.1 206.9 253.0 281.1302.3 327.1355.2 377.0 50 100 150 200 250 300 350 400

100.0 188.1 NN

75.0 CF3

50.0

25.0 230.1 56.1 145.1 73.1 172.0 42.1 95.0 127.1 159.1 211.1 0.0 252.9281.1 327.0 355.1 50 100 150 200 250 300 350 400

(D) 1-(3-METHYLPHENYL)PIPERAZINE (mMPP) 8.898mins

100.0 86.1

NN 75.0

CH3 50.0

207.0 25.0 281.0 57.1 99.1 207.9 252.9 135.1 326.9 387.1 0.0 177.0 236.9 295.0 50 100 150 200 250 300 350 400 (E) 1-(4-METHYLPHENYL)PIPERAZINE (pMPP) 8.898mins

100.0 134.1

NN CH3 75.0

50.0

176.1 25.0 91.1 119.1 56.1 41.1 0.0 159.1 207.0 253.0281.0 341.1 50 100 150 200 250 300 350 400

(F) 1-(2-CHLOROPHENYL)PIPERAZINE (oCPP) 8.943mins

100.0 154.1 NN

75.0 Cl

50.0

25.0 196.1 56.1 138.1 77.0 111.0 42.1 91.0 281.1 0.0 168.1 207.9236.9253.0 295.1 327.1 355.0 388.9 50 100 150 200 250 300 350 400 (G) 1-(2-METHOXYPHENYL)PIPERAZINE (oMeOPP) 8.943mins

100.0 150.1 NN 75.0

CH3O

50.0 192.1 135.1 25.0 56.1 120.1 42.1 77.1 0.0 176.1 207.9 252.9281.0 326.9 389.0 50 100 150 200 250 300 350 400

(H) 1-(3-CHLOROPHENYL)PIPERAZINE (mCPP) 9.325mins

100.0 154.1 NN 75.0 Cl

50.0

196.0 73.1 25.0

56.1 138.0 111.0 281.0 95.9 208.0 252.9 0.0 180.8 296.3 327.0 355.1 50 100 150 200 250 300 350 400 (I) 1-(4-METHOXYPHENYL)PIPERAZINE (pMeOPP) 9.325mins

100.0 150.1

NN OCH3 75.0

50.0

192.1 25.0 135.1 56.1 73.192.0 42.1 281.1 0.0 177.0207.9 253.0 327.1 50 100 150 200 250 300 350 400

(J) 1-(4-CHLOROPHENYL)PIPERAZINE (pCPP) 9.325mins

100.0 154.1 NN Cl

75.0

50.0

196.1 25.0

56.1 138.0 73.0 111.0 42.1 89.1 281.0 0.0 179.1208.0 253.1327.0 355.0 377.0 50 100 150 200 250 300 350 400 (K) 1,4-DIBENZYLPIPERAZINE (DBZP) 10.768mins

100.0 91.0

NN 75.0

50.0

120.1 175.1 25.0 266.2 65.0 134.2 42.0 148.1 0.0 206.9 238.0 281.1 327.0354.1376.9 50 100 150 200 250 300 350 400 IMMUNOASSAY

100 micrograms / ml 10 micrograms / ml 1 microgram / ml mAMP AMP MET mAMP MET mAMP A BZP P N N P N P B pFPP P N N P N - C TFMPP N N N N N - D mMPP P N N P N - E pMPP P N N P N - F oCPP P N ?N P ?N - G oMeOPP N N N N N - H mCPP ?P N N N N - I pMeOPP P N N P N - J pCPP P N N P N - K DBZP ------

Test Cutoff mAMP Syva RapidTest d.a.u. Methylamphetamine 1 microgram / ml AMP Syva RapidTest d.a.u. Amphetamine 1 microgram / ml MET Acon Methylamphetamine 1 microgram / ml

P positive N negative - not tested Occurrence of the compounds in products found in UK

in UK tablets/capsules A BZP Yes B pFPP Yes C TFMPP Yes D mMPP No E pMPP No F oCPP No G oMeOPP No H mCPP Yes I pMeOPP Yes J pCPP ? K DBZP Yes

Reaction with Marquis Reagent

Marquis reagent A BZP N B pFPP N C TFMPP N D mMPP N E pMPP N F oCPP N G oMeOPP very pale pink H mCPP N I pMeOPP N J pCPP N K DBZP O