FACT SHEET pcpp September 2016 For more information, please contact: Dr. P. Blanckaert Coordinator Belgian Early Warning System Drugs Scientific Institute of Public Health ational Focal Point on Drugs Jyliette Wytsmanstraat 14 B-1050 Brussels, Belgium Tel : 02/642 5408 bewsd@wiv-isp.be Science at the service of Public health, Food chain safety and Environment.
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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 ame p-chlorophenylpiperazine (pcpp) ature 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 ovember 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 FP 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 FP 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 FP reported 5 seizures of 22 tablets. Bulgaria: In March 2007 the FP 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 FP reported 1 seizure of 64 white tablets with "Crocodile" logo seized in Kardzhali in 2006. Bulgaria: In March 2007 the FP 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 FP 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 FP 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 FP reported 1 seizure of 260 white tablets, "heart" logo, seized in Varna in 2006. Tablets containing 1 MDMA. Bulgaria: In March 2007 the FP reported 1 seizure of 3 white tablets, Mitsubishi logo seized in Sofia in 2006. France: In ovember 2006 the FP 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: C 10 H 13 Cl 2 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. one 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. ot 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 A 1-benzylpiperazine C 11 H 16 2, mw 176 Sigma Aldrich 13815-25G-F BZP B C D E 1-(4-fluorophenyl)piperazine C 10 H 13 F 2, mw 180 Sigma Aldrich 19133-7 1-(3-trifluoromethylphenyl) piperazine m-trifluoromethylphenylpiperazine C 11 H 13 F 3 2, mw 230 1-(α,α,α-trifluoro-m-tolyl)piperazine Sigma Aldrich T8948 (HCl) 1-(3-methylphenyl)piperazine C 11 H 16 2, mw 176 Sigma Aldrich R435376 (dihcl) 1-(4-methylphenyl)piperazine C 11 H 16 2, mw 176 Sigma Aldrich 71868-5G-F pfpp F TFMPP CF 3 mmpp CH 3 pmpp CH 3 F 1-(2-chlorophenyl)piperazine C 10 H 13 Cl 2, mw 196.5 Sigma Aldrich C67605 (HCl) ocpp Cl G 1-(2-methoxyphenyl)piperazine C 11 H 16 2 O, mw 192 Sigma Aldrich M22601-5G (HCl) omeopp CH 3 O H 1-(3-chlorophenyl)piperazine C 10 H 13 Cl 2, mw 196.5 Sigma Aldrich 125180-5G (HCl) mcpp Cl I 1-(4-methoxyphenyl)piperazine C 11 H 16 2 O, mw 192 Sigma Aldrich 571415-1G (dihcl) pmeopp OCH 3 J 1-(4-chlorophenyl)piperazine C 10 H 13 Cl 2, mw 196.5 Sigma Aldrich C68008 pcpp Cl K 1,4-dibenzylpiperazine C 18 H 22 2, mw 266.4 Sigma Aldrich S383937-1EA (dihcl) DBZP
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 C/min 290 C 10.75 minutes
Chromatogram:- 1.00 (x10,000,000) TIC I.S (D),(E) 8.898 8.943 (F),(G) 168 I.S 0.75 7.444 (B),(C) (A) 8.478 8.554 9.325 (H),(I),(J) 0.50 0.25 0 7.0 7.5 8.0 8.5 9.0 9.5 1 10.5 11.0 ID Compound ame Abbreviations Retention time (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) - 168 K 1,4-dibenzylpiperazine DBZP 10.768 (not shown)
(A) BEZYLPIPERAZIE (BZP) 8.478mins 91.1 134.1 5 56.1 42.1 85.1 176.1 120.1 161.2 207.0 252.9 281.0 326.9 (B) 1-(4-FLUOROPHEYL)PIPERAZIE (pfpp) 8.554mins 138.1 F 5 180.1 122.1 56.1 95.0 42.0 150.1 206.9 253.0 281.1 302.3 327.1 355.2 377.0
(C) m-trifluoromethylpheylpiperazie (TFMPP) 8.554mins 188.1 CF 3 5 230.1 56.1 145.1 73.1 172.0 42.1 95.0 127.1 159.1 211.1 252.9 281.1 327.0 355.1 (D) 1-(3-METHYLPHEYL)PIPERAZIE (mmpp) 8.898mins 86.1 CH 3 5 207.0 281.0 57.1 99.1 135.1 207.9 252.9 177.0 236.9 295.0 326.9 387.1
(E) 1-(4-METHYLPHEYL)PIPERAZIE (pmpp) 8.898mins 134.1 CH 3 5 176.1 91.1 119.1 56.1 41.1 159.1 207.0 253.0 281.0 341.1 (F) 1-(2-CHLOROPHEYL)PIPERAZIE (ocpp) 8.943mins 154.1 Cl 5 196.1 56.1 138.1 42.1 77.0 111.0 91.0 168.1 207.9 236.9253.0 281.1 295.1 327.1 355.0 388.9
(G) 1-(2-METHOXYPHEYL)PIPERAZIE (omeopp) 8.943mins 150.1 CH 3 O 5 135.1 192.1 56.1 120.1 42.1 77.1 176.1 207.9 252.9 281.0 326.9 389.0 (H) 1-(3-CHLOROPHEYL)PIPERAZIE (mcpp) 9.325mins 154.1 Cl 5 73.1 196.0 56.1 111.0 138.0 281.0 95.9 180.8 208.0 252.9 296.3 327.0 355.1
(I) 1-(4-METHOXYPHEYL)PIPERAZIE (pmeopp) 9.325mins 150.1 OCH 3 5 192.1 135.1 56.1 73.192.0 42.1 177.0 207.9 253.0 281.1 327.1 (J) 1-(4-CHLOROPHEYL)PIPERAZIE (pcpp) 9.325mins 154.1 Cl 5 196.1 56.1 138.0 73.0 111.0 42.1 89.1 179.1 208.0 253.1 281.0 327.0 355.0377.0
(K) 1,4-DIBEZYLPIPERAZIE (DBZP) 10.768mins 91.0 5 120.1 175.1 134.2 266.2 42.0 65.0 148.1 206.9 238.0 281.1 327.0354.1376.9
IMMUOASSAY 100 micrograms / ml 10 micrograms / ml 1 microgram / ml mamp AMP MET mamp MET mamp A BZP P P P B pfpp P P - C TFMPP - D mmpp P P - E pmpp P P - F ocpp P? P? - G omeopp - H mcpp?p - I pmeopp P P - J pcpp P P - 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 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 o E pmpp o F ocpp o G omeopp o H mcpp Yes I pmeopp Yes J pcpp? K DBZP Yes Reaction with Marquis Reagent Marquis reagent A BZP B pfpp C TFMPP D mmpp E pmpp F ocpp G omeopp very pale pink H mcpp I pmeopp J pcpp K DBZP O
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. one 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. ot 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 A 1-benzylpiperazine C 11 H 16 2, mw 176 Sigma Aldrich 13815-25G-F BZP B C D E 1-(4-fluorophenyl)piperazine C 10 H 13 F 2, mw 180 Sigma Aldrich 19133-7 1-(3-trifluoromethylphenyl) piperazine m-trifluoromethylphenylpiperazine C 11 H 13 F 3 2, mw 230 1-(α,α,α-trifluoro-m-tolyl)piperazine Sigma Aldrich T8948 (HCl) 1-(3-methylphenyl)piperazine C 11 H 16 2, mw 176 Sigma Aldrich R435376 (dihcl) 1-(4-methylphenyl)piperazine C 11 H 16 2, mw 176 Sigma Aldrich 71868-5G-F pfpp F TFMPP CF 3 mmpp CH 3 pmpp CH 3 F 1-(2-chlorophenyl)piperazine C 10 H 13 Cl 2, mw 196.5 Sigma Aldrich C67605 (HCl) ocpp Cl G 1-(2-methoxyphenyl)piperazine C 11 H 16 2 O, mw 192 Sigma Aldrich M22601-5G (HCl) omeopp CH 3 O H 1-(3-chlorophenyl)piperazine C 10 H 13 Cl 2, mw 196.5 Sigma Aldrich 125180-5G (HCl) mcpp Cl I 1-(4-methoxyphenyl)piperazine C 11 H 16 2 O, mw 192 Sigma Aldrich 571415-1G (dihcl) pmeopp OCH 3 J 1-(4-chlorophenyl)piperazine C 10 H 13 Cl 2, mw 196.5 Sigma Aldrich C68008 pcpp Cl K 1,4-dibenzylpiperazine C 18 H 22 2, mw 266.4 Sigma Aldrich S383937-1EA (dihcl) DBZP
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 C/min 290 C 10.75 minutes
Chromatogram:- 1.00 (x10,000,000) TIC I.S (D),(E) 8.898 8.943 (F),(G) 168 I.S 0.75 7.444 (B),(C) (A) 8.478 8.554 9.325 (H),(I),(J) 0.50 0.25 0 7.0 7.5 8.0 8.5 9.0 9.5 1 10.5 11.0 ID Compound ame Abbreviations Retention time (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) - 168 K 1,4-dibenzylpiperazine DBZP 10.768 (not shown)
(A) BEZYLPIPERAZIE (BZP) 8.478mins 91.1 134.1 5 56.1 42.1 85.1 176.1 120.1 161.2 207.0 252.9 281.0 326.9 (B) 1-(4-FLUOROPHEYL)PIPERAZIE (pfpp) 8.554mins 138.1 F 5 180.1 122.1 56.1 95.0 42.0 150.1 206.9 253.0 281.1 302.3 327.1 355.2 377.0
(C) m-trifluoromethylpheylpiperazie (TFMPP) 8.554mins 188.1 CF 3 5 230.1 56.1 145.1 73.1 172.0 42.1 95.0 127.1 159.1 211.1 252.9 281.1 327.0 355.1 (D) 1-(3-METHYLPHEYL)PIPERAZIE (mmpp) 8.898mins 86.1 CH 3 5 207.0 281.0 57.1 99.1 135.1 207.9 252.9 177.0 236.9 295.0 326.9 387.1
(E) 1-(4-METHYLPHEYL)PIPERAZIE (pmpp) 8.898mins 134.1 CH 3 5 176.1 91.1 119.1 56.1 41.1 159.1 207.0 253.0 281.0 341.1 (F) 1-(2-CHLOROPHEYL)PIPERAZIE (ocpp) 8.943mins 154.1 Cl 5 196.1 56.1 138.1 42.1 77.0 111.0 91.0 168.1 207.9 236.9253.0 281.1 295.1 327.1 355.0 388.9
(G) 1-(2-METHOXYPHEYL)PIPERAZIE (omeopp) 8.943mins 150.1 CH 3 O 5 135.1 192.1 56.1 120.1 42.1 77.1 176.1 207.9 252.9 281.0 326.9 389.0 (H) 1-(3-CHLOROPHEYL)PIPERAZIE (mcpp) 9.325mins 154.1 Cl 5 73.1 196.0 56.1 111.0 138.0 281.0 95.9 180.8 208.0 252.9 296.3 327.0 355.1
(I) 1-(4-METHOXYPHEYL)PIPERAZIE (pmeopp) 9.325mins 150.1 OCH 3 5 192.1 135.1 56.1 73.192.0 42.1 177.0 207.9 253.0 281.1 327.1 (J) 1-(4-CHLOROPHEYL)PIPERAZIE (pcpp) 9.325mins 154.1 Cl 5 196.1 56.1 138.0 73.0 111.0 42.1 89.1 179.1 208.0 253.1 281.0 327.0 355.0377.0
(K) 1,4-DIBEZYLPIPERAZIE (DBZP) 10.768mins 91.0 5 120.1 175.1 134.2 266.2 42.0 65.0 148.1 206.9 238.0 281.1 327.0354.1376.9
IMMUOASSAY 100 micrograms / ml 10 micrograms / ml 1 microgram / ml mamp AMP MET mamp MET mamp A BZP P P P B pfpp P P - C TFMPP - D mmpp P P - E pmpp P P - F ocpp P? P? - G omeopp - H mcpp?p - I pmeopp P P - J pcpp P P - 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 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 o E pmpp o F ocpp o G omeopp o H mcpp Yes I pmeopp Yes J pcpp? K DBZP Yes Reaction with Marquis Reagent Marquis reagent A BZP B pfpp C TFMPP D mmpp E pmpp F ocpp G omeopp very pale pink H mcpp I pmeopp J pcpp K DBZP O