International Quality Assurance Programme (Iqap)

INTERNATIONAL QUALITY ASSURANCE PROGRAMME (IQAP)

INTERNATIONAL COLLABORATIVE EXERCISES (ICE)

Summary Report

BIOLOGICAL SPECIMENS 2018/1 INTERNATIONAL QUALITY ASSURANCE PROGRAMME (IQAP) INTERNATIONAL COLLABORATIVE EXERCISES (ICE) Table of contents Introduction Page 3 Comments from the International Panel of Forensic Experts Page 3 NPS reported by ICE participants Page 5 Codes and Abbreviations Page 8 Sample 1 Analysis Page 9 Identified substances Page 9 Statement of findings Page 10 Identification methods Page 15 Summary Page 18 Z-Scores Page 19 Sample 2 Analysis Page 22 Identified substances Page 22 Statement of findings Page 24 Identification methods Page 29 Summary Page 32 Z-Scores Page 33 Sample 3 Analysis Page 36 Identified substances Page 36 Statement of findings Page 38 Identification methods Page 43 Summary Page 46 Z-Scores Page 47 Sample 4 Analysis Page 52 Identified substances Page 52 Statement of findings Page 53 Identification methods Page 58 Summary Page 61 Z-Scores Page 62 Test Samples Information Samples Comments on samples Sample 1 To prepare BS-1, urine was spiked with an aqueous solution of gamma-hydroxybutyric acid (16490ng base/ml). The spiked urine was dispensed in 50ml aliquots and lyophilised.

Sample 2 To prepare BS-2, urine was spiked with an aqueous solution of morphine sulphate (1150ng base/ml). The spiked urine was dispensed in 50ml aliquots and lyophilised.

Sample 3 To prepare BS-3, urine was spiked with an acetonitrile solution of 6-monoacetylmorphine (690ng base/ml) and an aqueous solution of nordazepam (2300 ng base /ml). The spiked urine was dispensed in 50ml aliquots and lyophilised. Sample 4 To prepare BS-4, urine was spiked with an aqueous solution of mephedrone hydrochloride (86ng base/ml). The spiked urine was dispensed in 50ml aliquots and lyophilised.

Samples Substances Concentrations Comments on substances Sample 1 gamma-Hydroxybutyric acid (GHB) 16490 ng/ml Sample 2 Morphine (Total) 1150 ng/ml Sample 3 6-Monoacetylmorphine (6-MAM) 690 ng/ml Nordazepam 2300 ng/ml Sample 4 Mephedrone 86 ng/ml

This report contains the data received from laboratories participating in the current exercise. The results compiled in this report are not intended to be an overview of the quality of work and cannot be interpreted as such. These comments do not reflect the general state of the art within the profession.

Participant results are reported using a randomly assigned "WebCode". This code maintains participant's anonymity, provides linking of the various report sections, and will change with every report.

An important element of the UNODC International Quality Assurance Programme (IQAP) is the implementation of the International Collaborative Exercises (ICE). The exercises allow laboratories, from both developing and developed countries to continuously monitor their performance in drug testing on a truly global scale. This report provides information on analytical results of laboratories participating in the Seized Materials (SM) group. In order to maintain confidentiality, the participating laboratories have been assigned random “Web Codes”, which change every round.

The analytical results returned by laboratories participating in ICE are evaluated by UNODC and a confidential report is provided to each laboratory on its own performance. The overall analytical results are reviewed by the UNODC’s International Panel of Forensic Experts which oversees the implementation of these exercises, and offers guidance and support in addressing relevant quality issues. The exercises provide an overview of the performance and capacity of participating laboratories and enable UNODC to tailor technical support in the laboratory sector for greatest impact.

The ICE programme is a UNODC mandated activity and is implemented through regular budget funds and through the UNODC Global Scientific and Forensic Programme – Support Project (GLOU54), which operationalizes the forensic aspects of the UNODC Thematic Programme on Research, Trend Analysis and Forensics"

Continuous participation in the ICE programme

The continuous participation of laboratories in the UNODC International Collaborative Exercises (ICE) programme is a reflection of their consideration of the importance, laboratory quality assurance and continuous monitoring of performance plays in assuring the quality and reliability of test results. In particular, emphasizing that the quality and reliability of those results are a matter of safeguarding human rights and fundamental freedoms and ensuring public safety and effective law enforcement.

In recognition of this continuous participation, UNODC and its International Panel of Forensic Experts have decided to award certificates of participation to laboratories who successfully participate in four successive rounds of the ICE programme. It is worthwhile noting that approximately 30 laboratories have participated in every round of the ICE programme since its inception in 1995. UNODC would like to acknowledge and express its gratitude to these laboratories for their continued collaboration and valuable contribution to the development and success of the programme.

Comments from the International Panel of Forensic Experts

Participation of Laboratories

In the 2018/1 round of the ICE programme, results were submitted within both the Seized Materials (SM) and Biological Specimens (BS) test groups by 240 laboratories in 70 countries. Within the BS test group, results were submitted by 91 laboratories from 44 countries and within the SM test group, there were 201 participating laboratories from 70 countries.

Qualitative Analysis

The analytical technique most commonly used for screening of test samples in the BS test group were enzyme immunoassays (60% of participants), while GC-MS (74%) was the most commonly used technique for identification/confirmation of the components in the test samples. The results for the qualitative identification of the sample components in the BS test group, the number of false positive/negative results and the analyses not performed are shown in table 1.

3 Table 1. Qualitative performance of participants in the 2018/1 round of ICE.

BS-1 BS-2 BS-3 BS-3 BS-4 Test sample GHB Morphine 6-monoacetylmorphine Nordazepam Mephedrone Correct 27% 86% 82% 89% 32% identification Number of false 1 0 5 5 positives Number of false 13 3 3 33 negatives Number of analyses not 54 10 4 30 performed (ANP)

In general, the number of false positives reported for the four test samples was quite low. BS-3 contained 6- monoacetylmorphine (a specific metabolite indicative of heroin use) and nordazepam, however, thirty laboratories identified morphine in the sample. We are not considering this result a false positive as it is possible that during storage of the sample some hydrolysis of 6-MAM may have occurred and/or hydrolysis may also have occurred due to experimental conditions during analysis However, it is recommended that laboratories ensure appropriate storage and analytical conditions to avoid sample degradation.

The number of false negative results and analyses not performed for GHB and mephedrone in BS-1 and BS- 4 respectively are concerning and laboratories reporting false positive or false negative results should investigate the reasons for this and corrective actions should be taken in order to continuously improve performance. ICE participants are reminded that test samples can contain any of the substances in the ICE menu and as such if methods are available, all substances should be considered.

Quantitative Analysis

The test samples in the BS group for the 2018/1 round of ICE contained a total of five components and 39 (43%) of participating laboratories performed quantification. Of these laboratories, it is encouraging to note that 82% of laboratories quantified at least two components and 23% performed quantification of at least three test sample. GC-MS was used by 62% of participants for quantification, followed by LC/MS(/MS), which was used by 44% of participants. z-scores obtained by participants in quantification are shown in the table below (percentage + no. of labs indicated).

Table 2. Quantitative performance of participants in the 2018/1 round of ICE.

Test sample z-score BS-1 BS-2 BS-3 BS-3 BS-4 (GHB) (Morphine) (6-MAM) (Nordazepam) (Mephedrone) |z| < 2, 75% (12) 82% (28) 94% (29) 90% (28) 73% 8) satisfactory 2 ≤ |z| ≤ 3, 6% (1) 12% (4) 6% (2) 3% (1) - questionable |z| > 3, 19% (3) 6% (2) - 6% (2) 27% (3) unsatisfactory

According to the recommendations in ISO 13528:2005, an unsatisfactory z-score is considered to give an action signal and a questionable z-score is considered to give a warning signal. A single action signal or warning signals in two successive rounds shall be taken that an anomaly has occurred that requires investigation. Participants with z-scores outside acceptable limits should review their quantification procedures.

Of the seven laboratories that obtained a single action or warning signal in ICE rounds 2017/1 and 2017/2, five participated in 2018/1 and three of these improved their performance in quantitation. The laboratories C6JVZQ and POVZUG also obtained action or warning signals in 2018/1.

4 The following laboratories obtained a single action signal or warning signal in the two successive rounds of 2017/2 and 2018/1 and shall take this as anomaly, which requires further investigation: AGXHTY, C6JVZQ, KKJI6E and POVZUG.

Laboratories that need to perform quantitation routinely are encouraged to participate regularly in external proficiency testing or collaborative exercises such as the ICE programme. This will enable laboratories to assess the quality of their quantitative methods through the z-score values obtained. Laboratories reporting false positive or false negative results should investigate the root causes and corrective actions taken promptly in order to continuously improve performance. Participation in the ICE programme also helps in monitoring the effect of corrective actions. UNODC would like to acknowledge the valuable contribution of the Chemical Metrology Laboratory of the Health Sciences Authority, Singapore, for the provision of specific software used for the quantitative statistical calculations in the ICE programme.

New Psychoactive Substances (NPS) reported by laboratories participating in the 2018/1 round of the ICE programme

During the 2018/1round of ICE, participating laboratories provided information on NPS that had been identified in their laboratories. In total there were 143 reports of 103 substances. The most commonly reported substances were synthetic cannabinoids (28%) followed by “other substances” as shown in figure 1.

3% 7%

28% Synthetic cannabinoids 13% Synthetic cathinones

Other substances

Phenethylamines

Phencyclidine-type substances Tryptamines

27% 22%

Figure 1. NPS reported by ICE laboratories during the 2018/1 round of ICE

In terms of the mode of action of the NPS reported by ICE participants, the predominant substances reported were stimulants (32%), while 27% were synthetic cannabinoid receptor agonists (SCRA) and 17% were synthetic opioids (which included nine fentanyl derivatives) as shown in figure 2. 2% 7%

Stimulants 15% 32% SCRA

Opioids

Hallucinogens

Dissociatives

Sedatives/Hypnotics

17%

27%

Figure 2. Mode of action of NPS reported by ICE participants in the 2018/1 round of ICE

NPS most commonly reported by laboratories participating in ICE 2018/1

The substance most often reported by ICE participants was the synthetic cannabinoid receptor agonist 5F-MDMB-PINACA (methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3- dimethylbutanoate, followed by ketamine and then the synthetic opioid methoxyacetylfentanyl ( 2- methoxy-N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide) and the synthetic cannabinoid receptor agonist, AMB-FUBINACA (methyl (1-(4-fluorobenzyl)-1H-indazole-3-carbonyl)valinate) were both equally reported. For further details on these substances and others reported to the UNODC Early Warning Advisory, ICE participants can log on to the UNODC ICE portal and select the icon for the Early Warning Advisory on New Psychoactive substances as shown below.

6 INTERNATIONAL QUALITY ASSURANCE PROGRAMME (IQAP) INTERNATIONAL COLLABORATIVE EXERCISES (ICE)

Codes and Abbreviations

(+) “positive”: Indicates that the analyte is identified; for presumptive tests (e.g. colour reactions), indicates that a positive reaction was obtained. (-) “negative”: Indicates that the analyte is not identified.

(ANP): Analysis not performed.

Tech Code Name 100 Agglutination Techniques 110 Enzyme Immunoassay Techniques 120 Fluorescence Polarization Immunoassay 130 Radioimmunoassay 140 Colorimetric reactions 141 Marquis reagent (sulphuric acid, formaldehyde) 142 Cobalt thiocyanate 150 Thin Layer Chromatography 160 High/Ultra High Performance Liquid Chromatography 161 High Performance Liquid Chromatography with diode array detection 170 Gas Chromatography NPD 171 Gas Chromatography FID 172 Gas Chromatography ECD 180 Gas Chromatography/Mass Spectrometry 190 Fourier Transform Infrared Spectrometry 200 Spectrophotometry (visible, UV) 210 Others (specify) 211 NMR 220 Microcrystal test 230 Liquid chromatography/mass spectrometry 231 Liquid chromatography/tandem mass spectrometry

Sample 1 Analysis

Identified substances for Test Sample 1

Code Identified Substances 0VDD9G GHB 35XDDI GHB 3BSMFK GHB 3UYPY3 Not detected 48QEE4 Gamma hydroxybuturic acide (GHB) 4E7ZIJ - 64XLPQ GHB 7CAH7X GHB 7HJS9Q Caffeine 7NUSSC No drug AGXHTY GHB C6JVZQ None D6Q06A GHB DXXYXX None F9Q8GB GHB FXQFEB gamma-Hydroxybutyric acid (GHB) HKEKZQ GHB IPQ2PX GHB KKJI6E none KU9BHP No drugs LQLGLM GHB LVQGGU GHB M7F7FP none MMMMG5 - OBVQVP GHB PI4IFI None POVZUG GHB Q38299 THC-COOH and CODEINE RBYOV1 GHB RSAONM GHB RY77T7 - SJFHU7 NO FOUND ABUSE DRUGS SKR23G None TSQPSQ gamma-Hydroxybutyric acid (GHB) VYUQPU gamma-Butyrolactone (GBL) X328WA GHB XI4B45 GHB ZGZFSZ GHB

Statement of findings for Test Sample 1

Code gamma- Hydroxybutyric acid (GHB) 0KT0UD ANP

0VDD9G + The presence of GHB in the sample indicates consumption of GHB or a metabolic precursor. 11O1XT ANP

220U22 ANP The presence of drugs or psychotropic drugs was not detected in the analyzed sample. 35XDDI + Gammahydroxybutyrate ~20.3 mg/L 3BSMFK +

3UYPY3 ANP It was not detected the searched substances according the results. 48QEE4 + general extraction, identification and confirmation with GC/MS 4E7ZIJ ANP - 5I5O5B +

64XLPQ +

6EEUE1 ANP

70YAAL ANP Sample tested negative for Enzyme immunoassay screening for Drugs of abuse, no confirmation tests needed. 7CAH7X + The sample contains GHB. 7GH9UT ANP

7HJS9Q - Caffeine it´s a controlled substance in México. 7NUSSC - No drugs have been found 8BJ88Q ANP sample negative 8CHL4D ANP

99LN9D ANP No common drugs were detected in sample 2018/1/BS-1. 9D99UW - The sample 2018/1/BS-1 was analyzed for benzodiazepines, cocaine, amfetamines GHB/GBL and do not found to contain the drugs ot those groups. 9NRNMD ANP

Code gamma- Hydroxybutyric acid (GHB) A3V9ZR ANP

A9WZZV ANP

AEEU0E +

AGXHTY + GHB or Gamma Hydroxybutyrate is a central nervous system (CNS) depressant that is commonly referred to as a “club drug” or “date rape” drug. GHB is abused by teens and young adults at bars, parties, clubs and “raves” (all night dance parties), and is often placed in alcoholic beverages. Euphoria, increased sex drive, and tranquility are reported positive effects of GHB abuse. Negative effects may include sweating, loss of consciousness, nausea, hallucinations, amnesia, and coma, among other side effects. C6JVZQ ANP Caffeine and Theobromine CWRLNL +

CYQZSY ANP

D6Q06A + More than endogen value. DDDDB7 ANP

DDIM3Y ANP

DTDBJJ ANP Test sample 2018/1/BS-1 does not contain controlled drugs therefore Negative for Screening and Confirmatory analyses. DTRRZK ANP

DXXYXX ANP In sample BS-1 no drugs or metabolites were found EMMMOU ANP Common drugs not detected. EQUPXX ANP The substances that were tested for weren´t found to be present in the sample analysed. F9Q8GB + Drug detected using MS/MS with a ABSCiex 3200, negative mode, ionization source - electron spray. Results compared to those of a GHB standard injected under the same conditions. FXHPFX ANP

FXQFEB + gamma-Hydroxybutyric acid (GHB) was identified by GC/MS GK5SOG ANP

HKEKZQ +

HTTTKJ ANP

Code gamma- Hydroxybutyric acid (GHB) IMDPB5 ANP Drugs not detected IPQ2PX + Sample is positive for gamma-Hydroxybutyric acid JAD7AR ANP Analyzed drugs were not detected JJVUJ4 ANP

K0UCFK ANP

K2222R ANP

KHAFAU ANP

KJEYDH ANP

KKJI6E ANP negative KU9BHP ANP The sample SM1 does not contain any substance from ICE menu. LQLGLM + GHB was found in urine. GHB is a CNS depressant. LVQGGU +

M7F7FP ANP none MDDHDD - Normal MMMMG5 ANP Sample 2018/1/BS-1 negative. OBVQVP + Use of GHB, GBL or 1,4-butanediol. OGYYMJ - blank OQOODA -

PI4IFI ANP Sample 2018/1/BS-1 found not to contain any drugs POVZUG + Presence of GHB PXMPP5 ANP IN THE SAMPLE BS-1 WAS NOT FOUND CONTROLLED DRUGS Q38299 ANP

Q4CEQC ANP

Code gamma- Hydroxybutyric acid (GHB) QAHFEE -

QQQQNH ANP No Found to contain drugs QSQIQY ANP No drugs detected in BS1 sample. RBYOV1 + exogenous consumption RSAONM + Positive to gamma-hydroxybutyric acid (GHB) RY77T7 ANP - S06SXR ANP

S6LL6A ANP

SJFHU7 ANP IN THE SAMPLE NO FOUND ABUSE DRUGS SKR23G - No drugs were detected in BS-1, 2018/1 exercise. SSDJFL ANP

SVVVQE -

TSQPSQ + - U7TYIH ANP Se relalizo prueba de orientacion (cod.110) para AMP/COC/THC; B20/TCA/BAR; MET/MOP; MDMA/MTD; con resultato negative para todos UUZZZU ANP

VJVDSU - Toxicological examination yielded negative result VRRGOL -

VYUQPU ANP GBL is uncontrolled substances WWYBNT ANP

X328WA +

XI4B45 + This person consumed GHB. Z6Z10Q ANP

ZCNK6F -

Code gamma- Hydroxybutyric acid (GHB) ZGZFSZ +

ZNZZSU ANP

Identification methods for Test Sample 1

Legend: S ... used for Screening I ... used for Identification SI ... used for both

Analytical Technique Codes Code 100 110 120 141 150 161 170 172 180 230 231 210 0KT0UD S SI I SI 0VDD9G S I I 11O1XT S I SI 220U22 SI SI I I 35XDDI S I I 3BSMFK SI S DOA MultiGnost 10 test ver.B 3UYPY3 S 48QEE4 I I S immunochromatographie 4E7ZIJ S SI I 5I5O5B S I I 64XLPQ S SI 6EEUE1 I S Imunoessay 70YAAL S I 7CAH7X SI 7GH9UT S I 7HJS9Q S I I 7NUSSC I I S chromatographic imunoassay 8BJ88Q S I 8CHL4D S I 99LN9D SI 9D99UW SI 9NRNMD I A3V9ZR I A9WZZV SI SI AEEU0E SI AGXHTY S I I C6JVZQ S I CWRLNL S I I CYQZSY S I D6Q06A S I I DDDDB7 I I DDIM3Y S I SI DTDBJJ I S DTK DTRRZK S I

Code 100 110 120 141 150 161 170 172 180 230 231 210 DXXYXX SI SI EMMMOU S I EQUPXX S I F9Q8GB S I FXHPFX I LC-QTOF FXQFEB S I GK5SOG S I I HKEKZQ S I I HTTTKJ S I IMDPB5 I IPQ2PX S I S LC-TOF JAD7AR S SI JJVUJ4 I I I Kinetic Interactions of Microparticles K0UCFK S I K2222R S I I KHAFAU SI I KKJI6E SI SFC-MS/MS KU9BHP I S Imunoassay LQLGLM S SI LVQGGU S I I M7F7FP I SI Dipro Drug lab screen MDDHDD S SI MMMMG5 S I S Randox Biochip Array technology OBVQVP I I S OGYYMJ S I OQOODA S I I PI4IFI SI POVZUG S SI SI PXMPP5 S SI I Q38299 S I I Q4CEQC I I SI QAHFEE S I QQQQNH S I QSQIQY S I RBYOV1 SI RSAONM S SI RY77T7 S I SI S06SXR S

Code 100 110 120 141 150 161 170 172 180 230 231 210 S6LL6A SI SJFHU7 SI SKR23G SI SI SSDJFL S I SI SVVVQE S I TSQPSQ SI U7TYIH S UUZZZU I VJVDSU S SI I VRRGOL S I I VYUQPU S I I WWYBNT I X328WA I SI XI4B45 S I Z6Z10Q I S I ZCNK6F S I ZGZFSZ S I LC/QTOF ZNZZSU S I I

RESPONSE SUMMARY FOR TEST SAMPLE 1

Participants: 91

The response summary of all 91 participating laboratories for the identification of BS-1, frequency of use of screening and identification techniques and false positives and negatives:

Identification of Test Sample-1:

Substance Name Number of laboratories correctly identifying: GHB 25

False positives for Test Sample-1:

Round Code: Substance reported: Tech Code: Q38299 THC-COOH, Codeine 230/231

False negatives for Test Sample-1

Round Answer Tech Round Answer Tech Code: Code: Code: Code: Code: Code: OGYYMJ - 231 SKR23G - 231 QAHFEE - 150 MDDHDD - 180 7HJS9Q - 180 VJVDSU - 180 SVVVQE - 180 7NUSSC - 161/180 ZCNK6F - 180 OQOODA - 180/231 9D99UW - 180 VRRGOL - 180

The following fifty-four laboratories did not carry out analysis for GHB in test sample 1. UUZZZU, S06SXR, VYUQPU, RY77T7, DTDBJJ, C6JVZQ, QQQQNH, WWYBNT, CYQZSY, 8CHL4D, KJEYDH, JAD7AR, DXXYXX, 99LN9D, 8BJ88Q, PXMPP5, SJFHU7, 9NRNMD, 7GH9UT, A9WZZV, 0KT0UD, U7TYIH, KHAFAU, EQUPXX, 4E7ZIJ, 3UYPY3, KU9BHP, Z6Z10Q, Q38299, 220U22, 6EEUE1, DTRRZK, IMDPB5, PI4IFI, FXHPFX, KKJI6E, Q4CEQC, 70YAAL, DDIM3Y, 11O1XT, M7F7FP, K0UCFK, A3V9ZR, MMMMG5, SSDJFL, DDDDB7, K2222R, ZNZZSU, GK5SOG, JJVUJ4, QSQIQY. EMMMOU, S6LL6A and HTTTKJ

Frequency of use of screening, identification and quantification techniques:

Response Summary Participants 91 Technique 100 110 120 141 150 160 161 170 172 180 210 230 231 Screening (No.) 1 54 2 1 2 0 0 0 0 20 9 3 11

(%) 1.1 60.0 2.2 1.1 2.2 0.0 0.0 0.0 0.0 22.2 10.0 3.3 12.2

Identification (No.) 0 3 1 0 9 0 8 1 1 67 5 6 30 (%) 0.0 3.3 1.1 0.0 9.9 0.0 8.9 1.1 1.1 74.4 5.6 6.7 33.3

Quantification (No.) 0 0 0 0 0 1 2 0 1 24 2 2 17 (%) 0.0 0.0 0.0 0.0 0.0 2.6 5.1 0.0 2.6 61.5 5.1 5.1 43.6 17 Z-Score Report per Sample per Substance

Round: 2018/1 Robust average = 17580 ng/ml Substance: BS-1; GHB UNODC value = 16490 ng/ml

4.0 4.0 3.3

3.0

2.2 2.0

1.3

1.0 0.8

0.3

0.0 -4.8 0.0 -0.2 -0.1 -0.4 -0.6 -0.5 -1.0 -0.8 -0.8 -1.1

-2.0

-3.0

-4.0 ZGZFSZ 5I5O5B IPQ2PX 35XDDI 64XLPQ AEEU0E TSQPSQ RBYOV1 AGXHTY D6Q06A LQLGLM CWRLNL POVZUG X328WA OBVQVP LVQGGU

z-scores can be interpreted by participants in line with ISO 13528:2005, secion 7.4.2 and ISO/IEC guide43-1:1997(E) as follows: IzI < 2 = satisfactory 2 ≤ IzI ≤ 3 = questionable IzI > 3 = unsatisfactory According to the recommendations in ISO 13528:2005, an unsatisfactory z-score is considered to give an action signal and a questionable z-score is considered to give a warning signal. A single action signal or warning signal in two successive rounds shall be taken that an anomaly has occured that requires inverstigation.

18 Z-Score Report per Sample per Substance

Round: 2018/1 Substance: BS-1; GHB Dispersion of z-scores using different analytical techniques for the quantification of GHB in 2018/1 BS-1

4.0

3.0

2.0

1.0

0.0 Title

-1.0

-2.0

-3.0 GC-MS LC/MS

-4.0 HPLC GC-FID GC-MS/LC-MS

19 INTERNATIONAL QUALITY ASSURANCE PROGRAMME (IQAP) INTERNATIONAL COLLABORATIVE EXERCISES (ICE)

Z-Scores for Test Sample 1

GHB Code Concentration Deviation from z-score (ng/ml) robust average RBYOV1 1548 -16032 -4.8 LVQGGU 14000 -3580 -1.1 5I5O5B 15000 -2580 -0.8 64XLPQ 15000 -2580 -0.8 LQLGLM 15615 -1965 -0.6 ZGZFSZ 15991 -1589 -0.5 CWRLNL 16320 -1260 -0.4 X328WA 16890 -690 -0.2 IPQ2PX 17188 -392 -0.1 TSQPSQ 17500 -80 0.0 AEEU0E 18700 1120 0.3 35XDDI 20265 2685 0.8 OBVQVP 22000 4420 1.3 POVZUG 25000 7420 2.2 AGXHTY 28868 11288 3.3 D6Q06A 31000 13420 4.0

Sample 2 Analysis

Identified substances for Test Sample 2

Code Identified Substances 0KT0UD MORPHINE 0VDD9G Morphine 11O1XT Morphine 220U22 Morphine 35XDDI Morphine 3BSMFK morphine 3UYPY3 Not detected 48QEE4 Morphine 4E7ZIJ - 64XLPQ morphine 6EEUE1 Morphine 70YAAL Morphine 7CAH7X Morphine 7GH9UT morphine 7HJS9Q Morphine and Caffeine 7NUSSC morphine total 8BJ88Q morphine 8CHL4D morphine 9NRNMD Morphine A3V9ZR morphine A9WZZV Morphine (total) AGXHTY Morphine C6JVZQ Morphine Total CYQZSY MORPHINE D6Q06A morphine DDDDB7 morphine(total) DDIM3Y morphine DTDBJJ Morphine (Total) DTRRZK Morphine DXXYXX Morphine EQUPXX Morphine F9Q8GB Morphine FXHPFX Morphine FXQFEB Morphine (Total) HKEKZQ Morphine IMDPB5 Morphine IPQ2PX Morphine JAD7AR Morphine JJVUJ4 Morphine K2222R opiates

Code Identified Substances KHAFAU Morphine KJEYDH Morphine KKJI6E morphine KU9BHP Morphine LQLGLM Morphine LVQGGU Morphine M7F7FP Opiates MDDHDD Morphine MMMMG5 morphine OBVQVP Morphine OGYYMJ Morphine OQOODA Morphine PI4IFI None POVZUG morphine PXMPP5 MORPHINE Q38299 MORPHINE Q4CEQC morphine QAHFEE Morphine QQQQNH Morphine QSQIQY Morphine RBYOV1 Morphine RSAONM Morphine RY77T7 Morphine S6LL6A morphine SJFHU7 MORPHINE SKR23G Morphine SSDJFL Morphine SVVVQE morphine TSQPSQ Morphine (Total) UUZZZU morphine VJVDSU Morphine VYUQPU Morphine X328WA morphine XI4B45 Morphine Z6Z10Q morphine ZCNK6F morphine ZGZFSZ Morphine

Statement of findings for Test Sample 2

Code Morphine (Total) 0KT0UD +

0VDD9G + The presence of Morphine in the sample indicates morphine consumption or consumption of other opiates such codeine or heroine. 11O1XT +

220U22 + The presence of Morphine was detected in the sample. 35XDDI + Morphine, Total Detected >0.5mg/L 3BSMFK +

3UYPY3 ANP It was not detected the searched substances according the results. 48QEE4 + general extraction, identification and confirmation with HPLC/DAD 4E7ZIJ - - 5I5O5B +

64XLPQ +

6EEUE1 +

70YAAL + Sample tested positive for Opiates/ opioids Enzyme immunoassay screening for Drugs of abuse.

Morphine was confirmed and quantified at 418.55ng/ml 7CAH7X + The sample contains morphine. 7GH9UT +

7HJS9Q + Contains Morphine and Caffeine both controlled sustances in México. 7NUSSC + Opiat (morphine total) has been found 8BJ88Q + positive for morphine (total 700 ng/ml) 8CHL4D + screening positive opiates, CG/MS positive morphine 99LN9D ANP No common drugs were detected in sample 2018/1/BS-2. 9D99UW ANP The sample 2018/1/BS-2 was analyzed for benzodiazepines, cocaine, amfetamines GHB/GBL and do not found to contain the drugs ot those groups.

Code Morphine (Total) 9NRNMD + The coincidence between the retention time and the fragmantogram of a reference material analyzed under the same conditions of the sample indicate the presence of morphine in this. A3V9ZR + use of morphine A9WZZV + Analytical Adverse Finding for (total) morphine AEEU0E +

AGXHTY + Morphine is a opioid pain medication, used to treat moderate to severe pain C6JVZQ + Caffeine and Theobromine CWRLNL +

CYQZSY +

D6Q06A + Cafeine and paracetamol like adulterant. DDDDB7 +

DDIM3Y + previous use of morphine DTDBJJ + Test sample 2018/1/BS-2 was found to contain controlled drugs for Morphine (Total) therefore Positive for the Screening and Confirmatory analyses with concentration value of 1,177.38 ng/ml. DTRRZK + Morphine was detected using GC-MS which indicates use of controlled drug. DXXYXX + In sample BS-2 the drug Morphine was found EMMMOU ANP Common drugs not detected. EQUPXX + It was detected the presence of morphine in the sample analysed. F9Q8GB + Detected with a Bruker Impact Q-Tof in positive mode, ionization source - electron spray. Results compared to those of a morphine standard injected under the same conditions. FXHPFX + Morphine is a narcotic analgesic found in the opium poppy. It is Schedule II substance in the United States. FXQFEB + Morphine (Total) was identified by GC/MS GK5SOG ANP

HKEKZQ +

HTTTKJ -

IMDPB5 + Morphine detected

Code Morphine (Total) IPQ2PX + Sample is positive for Morphine JAD7AR + Urine Sample was found to contain 829 ng/mL Morphine JJVUJ4 + Morphine K0UCFK ANP

K2222R + morphine KHAFAU + Prior ingestion of Heroin/Morphine KJEYDH ANP Only free morphine was measured. KKJI6E + positive KU9BHP + Morphine was identified in the sample SM2 analyzed. This results mean that morphine or other opioids were used. LQLGLM + Morphine is detected in urine. This indicates intake of morphine, or heroine which is metabolized to morphine in the body. Morphine is an analgesic opiate. LVQGGU +

M7F7FP + We found Morphine MDDHDD + Morphine was detected by two GC/MS method with acid or enzymatic hydrolysis with final derivatization. The morphine should be quantified MMMMG5 + Sample 2018/1/BS-2 contain morphine. OBVQVP + Use of pure heroin or morphine. OGYYMJ +

OQOODA +

PI4IFI ANP Sample 2018/1/BS-2 found not to contain any drugs POVZUG + Presence of morphine PXMPP5 + IN THE SAMPLE BS-2 WAS FOUND MORPHINE Q38299 +

Q4CEQC +

Code Morphine (Total) QAHFEE +

QQQQNH + free QSQIQY + Morphine was detected in BS2 sample. RBYOV1 + morphine consumption RSAONM + Positive to morphine. RY77T7 +

S06SXR ANP

S6LL6A +

SJFHU7 + in the sample analyzed, presence of morphine was detected SKR23G + Morphine was detected in BS-2, 2018/1 exercise. SSDJFL + There was consumption of Morphine SVVVQE +

TSQPSQ + - U7TYIH ANP Se relalizo prueba de orientacion (cod.110) para AMP/COC/THC; B20/TCA/BAR; MET/MOP; MDMA/MTD; con resultato positivo solo para opiodes UUZZZU +

VJVDSU + Toxicological examination revealed the presence of morphine VRRGOL +

VYUQPU + we found morphine as narcotic substances WWYBNT +

X328WA +

XI4B45 + This person consumed morphine or heroin. Z6Z10Q + morphine ZCNK6F + after chemical analysis was performed the sample contained morphine

Code Morphine (Total) ZGZFSZ +

ZNZZSU -

Identification methods for Test Sample 2

Legend: S ... used for Screening I ... used for Identification SI ... used for both

RESPONSE SUMMARY FOR TEST SAMPLE 2

Participants: 91

The response summary of all 91 participating laboratories for the identification of BS-2, frequency of use of screening and identification techniques and false positives and negatives:

Identification of Test Sample-2:

Substance Name Number of laboratories correctly identifying: Morphine 77

False positives for Test Sample-2: There were no false positive results for test sample 2

False negatives for Test Sample-2 (techniques(s) used for ANP):

Round Code: Substance reported: Tech Code: HTTTKJ - 180 4E7ZIJ - 150/180 ZNZZSU - 150/180

The following ten laboratories did not carry out analysis for morphine in test sample 2: S06SXR, KJEYDH, 99LN9D, U7TYIH, 9D99UW, 3UYPY3, PI4IFI, K0UCFK, GK5SOG and EMMMOU

Frequency of use of screening, identification and quantification techniques:

Response Summary Participants 91 Technique 100 110 120 141 150 160 161 170 172 180 210 230 231 Screening (No.) 1 54 2 1 2 0 0 0 0 20 9 3 11

(%) 1.1 60.0 2.2 1.1 2.2 0.0 0.0 0.0 0.0 22.2 10.0 3.3 12.2

Identification (No.) 0 3 1 0 8 0 9 1 1 67 5 6 30 (%) 0.0 3.3 1.1 0.0 8.9 0.0 9.9 1.1 1.1 74.4 5.6 6.7 33.3

Quantification (No.) 0 0 0 0 0 1 2 0 1 24 2 2 17 (%) 0.0 0.0 0.0 0.0 0.0 2.6 5.1 0.0 2.6 61.5 5.1 5.1 43.6 31 Z-Score Report per Sample per Substance

Round: 2018/1 Robust average = 1009 ng/ml Substance: BS-2; Morphine UNODC value = 1150 ng/ml

4.0 3.6

3.0

2.2

2.0 1.7

0.9 1.0 1.0 0.7 0.7 0.8 0.6 0.6 0.4 0.4 0.4 0.5 0.2 0.2 0.3 0.3 0.0 0.0 0.0 -0.1 -0.1 -0.4 -1.0 -0.9 -0.8 -1.1 -1.3 -1.3 -1.5 -1.4 -2.0 -2.0

-2.5 -3.0 -2.8

-3.3

-4.0 KKJI6E JJVUJ4 SSDJFL XI4B45 DTDBJJ ZGZFSZ IPQ2PX RY77T7 8BJ88Q KJEYDH C6JVZQ 70YAAL 7HJS9Q Z6Z10Q ZCNK6F JAD7AR 64XLPQ SKR23G AEEU0E DTRRZK 7CAH7X TSQPSQ 0KT0UD RBYOV1 SVVVQE AGXHTY LQLGLM OGYYMJ CWRLNL A9WZZV POVZUG X328WA OBVQVP LVQGGU z-scores can be interpreted by participants in line with ISO 13528:2005, secion 7.4.2 and ISO/IEC guide43-1:1997(E) as follows: IzI < 2 = satisfactory 2 ≤ IzI ≤ 3 = questionable IzI > 3 = unsatisfactory According to the recommendations in ISO 13528:2005, an unsatisfactory z-score is considered to give an action signal and a questionable z- score is considered to give a warning signal. A single action signal or warning signal in two successive rounds shall be taken that an anomaly has occured that requires inverstigation.

32 Z-Score Report per Sample per Substance

Round: 2018/1 Substance: BS-2; Morphine Dispersion of z-scores using different analytical techniques for the quantification of Morphine in 2018/1 BS-2

10.0

8.0

6.0

4.0

2.0

0.0 Title

-2.0

-4.0

-6.0

-8.0 GC-MS LC/MS

-10.0 HPLC GC-FID GC-MS/LC-MS

33 INTERNATIONAL QUALITY ASSURANCE PROGRAMME (IQAP) INTERNATIONAL COLLABORATIVE EXERCISES (ICE)

Z-Scores for Test Sample 2

Morphine Deviation Code Concentration from z-score (ng/ml) robust average C6JVZQ 300 -709 -3.3 70YAAL 419 -590 -2.8 AEEU0E 476 -533 -2.5 Z6Z10Q 575 -434 -2.0 0KT0UD 698 -311 -1.5 8BJ88Q 700 -309 -1.4 KJEYDH 728 -281 -1.3 7CAH7X 737 -272 -1.3 SKR23G 765 -244 -1.1 RBYOV1 820 -189 -0.9 JAD7AR 829 -180 -0.8 LQLGLM 913 -96 -0.4 JJVUJ4 979 -30 -0.1 OBVQVP 995 -14 -0.1 SVVVQE 1005 -4 0.0 AGXHTY 1017 8 0.0 DTRRZK 1056 47 0.2 SSDJFL 1058 49 0.2 XI4B45 1065 56 0.3 ZGZFSZ 1072 63 0.3 A9WZZV 1100 91 0.4 TSQPSQ 1100 91 0.4 64XLPQ 1100 91 0.4 ZCNK6F 1120 111 0.5 IPQ2PX 1136 127 0.6 KKJI6E 1143 134 0.6 7HJS9Q 1162 153 0.7 OGYYMJ 1165 156 0.7 DTDBJJ 1177 168 0.8 X328WA 1210 201 0.9 LVQGGU 1216 207 1.0 CWRLNL 1372 363 1.7 RY77T7 1482 473 2.2 POVZUG 1775 766 3.6

Sample 3 Analysis

Identified substances for Test Sample 3

Code Identified Substances 0KT0UD MORPHINE, 6-MAM, NORDAZEPAM 0VDD9G 6-MAM and Nordazepam 11O1XT 6-MAM, nordiazepam 220U22 Nordazepam; Morphine 35XDDI 6MAM, Morphine, Nordiazepam 3BSMFK 6-MAM, nordazepam 3UYPY3 Not detected 48QEE4 Nordazepam 4E7ZIJ Nordazepam 64XLPQ 6-MAM and nordiazepam 6EEUE1 Nordiazepam-6MAM 70YAAL 6-Monoacetylmorphine and Nordazepam 7CAH7X 6-MAM, Morphine, Nordazepam 7GH9UT morphine, 6-MAM, nordazepam 7HJS9Q Nordazepam and 6-MAM 7NUSSC Nordiazepam 8BJ88Q 6-AM 8CHL4D morphine, 6-monoacetylmorphine, nordazepam 99LN9D Nordazepam and 6-Monoacetylmorphine (6-MAM) 9D99UW Nordazepam 9NRNMD Nordazepam, 6-Monoacetylmorphine A3V9ZR nordazepam, 6-monoacetylmorphine A9WZZV Nordiazepam ; MAM ; morphine AGXHTY 6-MAM, Morphine and nordazepam C6JVZQ Nordazepam, Morphine total and 6-MAM CYQZSY 6MAM, MORPHINE, NORDAZEPAM D6Q06A nordazepam, 6-MAM DDDDB7 nordazepam, 6-monoacetylmorphine DDIM3Y 6-mam and nordiazepam DTDBJJ Nordazepam, 6-MAM DTRRZK Morphine, Nordazepam, 6-monoacetylmorphine DXXYXX 6-Monoacetylmorphine, morphine and Nordazepam EMMMOU 6-MAM and nordazepam EQUPXX Morphine, 6-MAM, Nordazepam and fluconazole. F9Q8GB Nordazepam and 6-MAM FXHPFX 6-MAM, morphine, nordiazeapm FXQFEB Nordazepam, Morphine, 6-Monoacetylmorphine (6-MAM) GK5SOG Nordazepam and 6-MAM HKEKZQ Nordazepam HTTTKJ Nordazepam, 6-Monoacetylmorphine

Code Identified Substances IMDPB5 Nordazepam & 6-MAM IPQ2PX Nordazepam, 6-Monoacetylmorphine JAD7AR Nordiazepam, 6-MAM, Morphine JJVUJ4 Nordiazepam, Monoacetylmorphine K0UCFK Nordazepam K2222R opiates KHAFAU DMDZ, 6-MAM, Morphine KJEYDH 6-Monoacetylmorphine (6-MAM), Nordazepam KKJI6E nordazepam, 6-monoacetylmorphine KU9BHP 6-monoacetylmorphine and nordazepam LQLGLM Nordiazepam and 6-MAM LVQGGU 6-MAM, Morphine, Nordazepam M7F7FP Opiates, Benzodiazepines MDDHDD Diazepam and 6-MAM MMMMG5 codeine, 6-monoacetilmorphine,temazepam OBVQVP Nordazepam, 6-MAM OGYYMJ Nordiazepam and 6-Monoacetylmorphine (6-MAM) OQOODA Nordazepam and 6-Monoacetylmorphine (6-MAM) PI4IFI Nordazepam POVZUG 6-MAM and nordiazepam PXMPP5 6-MONOACETYLMORPHINE, NORDAZEPAM Q38299 MORPHINE, 6-MAM, NORDAZEPAM Q4CEQC morphine, 6-monoacetylmorphine QAHFEE Morphine, Benzoylecgonine QQQQNH 6-Monoacethylmophine and Nodiazepam QSQIQY 6-MAM and Nordazepam RBYOV1 nordiazepam and 6-MAM RSAONM Nordazepam and 6-monoacetylmorphine RY77T7 Nordazepam, 6-MAM S06SXR Opiates and Benzodiazepines S6LL6A codeine SJFHU7 6-MAM, NORDAZEPAM SKR23G Nordazepam, medazepam and 6-MAM SSDJFL Nordiazepam-6 MAM SVVVQE morphine, 6-MAM, nordazepam TSQPSQ Nordazepam ,6-Monoacetylmorphine (6-MAM) VJVDSU nordazepam and 6-Monoacetylmorphine VYUQPU 6-MAM and Nordazepam X328WA nordazepam, 6-MAM XI4B45 MAM, morphine, nordazepam Z6Z10Q morphine, 6-MAM, NORDAZEPAM ZCNK6F morphine - nordiazepam ZGZFSZ Nordazepam, 6-MAM ZNZZSU Morphine, MAM,Nordazepam

Statement of findings for Test Sample 3

Code 6- Monoacetylmorphin Nordazepam e (6-MAM) 0KT0UD + +

0VDD9G + + The presence of 6-MAM indicates heroin consumption. The nordazepam finding indicates consumption of benzodiazepines, which can come from the intake of nordazepam itself or as a metabolite from other benzodiazepines. 11O1XT + + It indicates the intake of heroin and either of diazepam or of nordiazepam. 220U22 - + The presence of Nordazepam and Morphine was detected in the sample. 35XDDI + + 6-Monoacetylmorphine (6MAM) ~0.5mg/L Morphine, Total ~0.04mg/L Nordiazepam Detected >1mg/L 3BSMFK + +

3UYPY3 ANP ANP It was not detected the searched substances because the lack of utilities for confirmation. 48QEE4 - + general extraction, identification and confirmation with HPLC/DAD 4E7ZIJ ANP + Nordazepam was identified in the sample. 5I5O5B + +

64XLPQ + +

6EEUE1 + +

70YAAL + + Sample tested positive for Opiates/ opioids and Benzodiazepines Enzyme immunoassay screening for Drugs of abuse.

6-MAM was confirmed and quantified at 687.68ng/ml.

Nordazepam was identified in the sample, however the latter was not quantified as it is not included in our laboratory's quantification test panel. 7CAH7X + + The sample contains 6-MAM, morphine and nordazepam. 7GH9UT + +

7HJS9Q + + The Sample BS-3 contains Nordazepam and 6 MAM. 7NUSSC - + Benzodiazepine (Nordiazepam) has been found 8BJ88Q + - positive for 6-monoacetylmorphine (400 ng/ml)

Code 6- Monoacetylmorphin Nordazepam e (6-MAM) 8CHL4D + + screening positive opiates and Benzodiazepine, CG/MS positive morphine,6-monoacetylmorphine, nordazepam 99LN9D + + Nordazepam and 6-Monoacetylmorphine (6-MAM) were detected in sample 2018/1/BS-3. 9D99UW ANP + Nordazepam was detected in the sample 2018/1/BS-3. 9NRNMD + + The coincidence between the retention time and the fragmantogram of a reference material analyzed under the same conditions of the sample indicate the presence of nodazepem and 6- monoacethylmorphine in this. A3V9ZR + + use of nordazepam, 6-MAM A9WZZV + + Analytical Adverse Finding for Mono-acetyl-morphine, morphine and nordiazepam. AEEU0E + +

AGXHTY + + The presence of morphine in a urinary sample may be causedonly by intake of heroin. 6- Monoacetylmorphine (6-MAM, 6-acetylmorphine, or 6-AM) is one of three active metabolites of heroin (diacetylmorphine), the others being morphine and the much less active 3- monoacetylmorphine (3-MAM). Nordazepam is a 1,4-benzodiazepine derivative. Like other benzodiazepine derivatives, it has amnesic, anticonvulsant, anxiolytic, muscle relaxant, and sedative properties. However, it is used primarily in the treatment of anxiety disorders. It is an active metabolite of diazepam, chlordiazepoxide, clorazepate, prazepam, pinazepam, and medazepam.

Nordazepam is among the longest lasting (longest half-life) benzodiazepines, and its occurrence as a metabolite is responsible for most cumulative side-effects of its myriad of pro-drugs when they are used repeatedly at moderate-high doses; the nordazepam metabolite oxazepam is also active , which contributes to nordazepam cumulative side-effects but occur too minutely to contribute to the cumulative side-effects of nordazepam pro-drugs ). C6JVZQ + + Caffeine, Theobromine and Fluconazol CWRLNL + +

CYQZSY + +

D6Q06A + + caffeine as adulterant. DDDDB7 + +

DDIM3Y + + previous use of heroin, and diazepam or chlordiazepoxide or nordiazepam DTDBJJ + + Test sample 2018/1/BS-3 was found to contain controlled drugs for Nordazepam and 6-MAM therefore Positive for the Screening and Confirmatory analyses with concentration values of 1,900.16 ng/ml for Nordazepam and 548.51 ng/ml for 6-MAM. DTRRZK + + Morphine, Nordazepam, 6-monoacetylmorphine were detected which indicates use of controlled drug.

Code 6- Monoacetylmorphin Nordazepam e (6-MAM) DXXYXX + + In sample BS-3 the drugs 6-Monoacetylmorphine, morphine (might be a by-product from 6- Monoacetylmorphine formed during the enzimatic hydrolysis) and Nordazepam were found EMMMOU + + 6-MAM and nordazepam detected. EQUPXX + + It was detected the presence of Morphine, 6-MAM, Nordazepam and fluconazole in the sample analysed. F9Q8GB + + Detected with a Bruker Impact Q-Tof in positive mode, ionization source - electron spray. Results compared to those of a nordazepam and 6-MAM standards injected under the same conditions. FXHPFX + + 6-monoacetylmorphine (6-MAM) is the 6-monoacetylated form of morphine, which is pharmacologically active. When present it is generally indicative of heroin (diacetylmorphine) use. Heroin is a schedule I substance in the United States. Morphine is a narcotic analgesic found in the opium poppy. It is Schedule II substance in the United States. Nordiazepam is a benzodiazepine derivative that can either be a parent drug or metabolite of diazepam. Nordiazepam is a schedule IV drug in the United States. FXQFEB + + Nordazepam, Morphine, 6-Monoacetylmorphine (6-MAM) were identified by GC/MS GK5SOG + + Nordazepam and 6-MAM detected HKEKZQ - +

HTTTKJ + +

IMDPB5 + + Nordazepam and 6-monoacetylmorphine detected. IPQ2PX + + Sample is positive for Nordazepam and 6-Monoacetylmorphine JAD7AR + + Urine sample was found to contain 1557 ng/mL Noridiazepam and 501 ng/mL 6-MAM. Morphine was also detected in trace amount JJVUJ4 + + Nordiazepam, Monoacetylmorphine K0UCFK ANP + The urine was analysed and found to contain nordazepam. K2222R + + morphine 6-monoacetylmorphine nordiazepam KHAFAU + + Prior ingestion of Heroin, Diazepam/chlordiazepoxide KJEYDH ANP ANP

KKJI6E + + positive KU9BHP + + 6-monoacetylmorphine and nordazepam were identified in the sample SM3 analyzed. Fluconazol was also identified, but it is not a psychotropic drug.

Code 6- Monoacetylmorphin Nordazepam e (6-MAM) LQLGLM + + Nordiazepam is a metabolite of diazepam, and could be explained by intake of diazepam: as it in addition can be taken as an individual drug an intake of nordiazepam or a combination of intake can not be ruled out.

6-MAM is a specific heroin metabolite and indicates intake of heroin. LVQGGU + +

M7F7FP - - We found codein and oxazepam. MDDHDD + + 6-MAM was detected by GC/MS method with enzymatic hydrolysis with final derivatization. The 6-MAM should be quantified Diazepam was detected by 3 different GC/MS method using two derivatization methods MMMMG5 + - Sample 2018/1/BS-3 contain codeine, 6-monoacetilmorphine,temazepam OBVQVP + + Nordazepam use. 6-MAM indicates heroin abuse, but the absence of morphine is suspicious. OGYYMJ + + Sample 2018/1/BS-3 contains Nordiazepam and 6-Monoacetylmorphine (6-MAM) OQOODA + +

PI4IFI ANP + Sample 2018/1/BS-3 found to contain Nordazepam POVZUG + + presence of 6-MAM and nordiazepam PXMPP5 + + IN THE SAMPLE BS-3 WAS FOUND 6-MONOACETYLMORPHINE AND NORDAZEPAM Q38299 + +

Q4CEQC + +

QAHFEE - -

QQQQNH + + free QSQIQY + + 6-MAM and Nordazepam were detected in BS3 sample. RBYOV1 + + benzodiazepine consumtion plus heroin consumption RSAONM + + Positive to Nordazepam (diazepam metabolite) and 6-monoacetylmorphine (heroin metabolite). RY77T7 + +

S06SXR ANP ANP

Code 6- Monoacetylmorphin Nordazepam e (6-MAM) S6LL6A - ANP There were two other drugs in this sample but according to our available standards we could not identify those. SJFHU7 + + in the sample analyzed, presence of 6-acetylmorphine and nordazepam was detected SKR23G + + Nordazepam, medazepam and 6-MAM were detected in BS-3, 2018/1 exercise. SSDJFL + + THERE WAS BENZODIAZEPINAS AND MORPHINE CONSUMPTION SVVVQE + +

TSQPSQ + + - U7TYIH ANP ANP Se relalizo prueba de orientacion (cod.110) para AMP/COC/THC; B20/TCA/BAR; MET/MOP; MDMA/MTD; con resultato positivo solo para benzodiacepinas y opiodes UUZZZU + ANP

VJVDSU + + Toxicological examination revealed the presence of nordazepam and 6-monoacetylmorphine VRRGOL + +

VYUQPU + + we found Nordazepam as psychotropic substances WWYBNT + +

X328WA + +

XI4B45 + + This person consumed heroin and 1,4-benzodiazepines (most likely diazepam). Z6Z10Q + + morphine, 6-MAM, NORDAZEPAM ZCNK6F - + after chemical analysis was performed the sample contained morphine -nordiazepam ZGZFSZ + +

ZNZZSU + +

Identification methods for Test Sample 3

Legend: S ... used for Screening I ... used for Identification SI ... used for both

RESPONSE SUMMARY FOR TEST SAMPLE 3

Participants: 91

The response summary of all 91 participating laboratories for the identification of BS-3, frequency of use of screening and identification techniques and false positives and negatives:

Identification of Test Sample-3:

Substance Name Number of laboratories correctly identifying: 6-monoacetylmorphine 75 Nordazepam 81

False positives for Test Sample-3:

Round Code: Substance reported: Tech Code: M7F7PF Codeine 150 MMMMG5 Temazepam, codeine 150 QAHFEE Benzoylecgonine 150 ZNZZSU Morphine-3-glucuronide 150/180 M7F7FP Oxazepam 150 MDDHDD Diazepam 180 SKR23G Medazepam 110/231

False negatives for both components of Test Sample-3 (techniques(s) used or ANP):

Round Code: Answer code Tech Code: M7F7PF - 150 QAHFEE - 150 3UYPY3 - ANP KJEYDH - ANP S06SXR - ANP U7TYIH - ANP

Frequency of use of screening, identification and quantification techniques:

Response Summary Participants 91 Technique 100 110 120 141 150 160 161 170 172 180 210 230 231 Screening (No.) 1 54 2 1 2 0 0 0 0 20 9 3 11

(%) 1.1 60.0 2.2 1.1 2.2 0.0 0.0 0.0 0.0 22.2 10.0 3.3 12.2

Identification (No.) 0 3 1 0 8 0 9 1 1 67 5 6 30 (%) 0.0 3.3 1.1 0.0 8.9 0.0 9.9 1.1 1.1 74.4 5.6 6.7 33.3

Quantification (No.) 0 0 0 0 0 1 2 0 1 24 2 2 17 (%) 0.0 0.0 0.0 0.0 0.0 2.6 5.1 0.0 2.6 61.5 5.1 5.1 43.6

45 Z-Score Report per Sample per Substance

Round: 2018/1 Robust average = 588 ng/ml Substance: BS-3; 6-monoacetylmorphine UNODC value = 690 ng/ml

4.0 3.8

3.2

3.0

2.3

2.0 1.5 1.2

1.0 0.7 0.8 0.6 0.4 0.5 0.2 0.2 0.2 0.3 0.0 0.1 0.1 0.0

-0.3 -0.2 -0.4 -0.3 -0.5 -0.5 -1.0 -0.7 -0.9 -1.1

-2.0 -1.9 -2.2

-3.0 -2.7 -3.1 -3.2

-4.0 KKJI6E JJVUJ4 SSDJFL XI4B45 DTDBJJ ZGZFSZ IPQ2PX 35XDDI RY77T7 KJEYDH 8BJ88Q C6JVZQ 70YAAL 7HJS9Q Z6Z10Q JAD7AR 64XLPQ SKR23G AEEU0E 0KT0UD TSQPSQ SVVVQE RBYOV1 AGXHTY LQLGLM OGYYMJ CWRLNL POVZUG X328WA OBVQVP LVQGGU

46 Z-Score Report per Sample per Substance

Round: 2018/1 Robust average = 18670 ng/ml Substance: BS-3; Nordazepam UNODC value = 2300 ng/ml

4.0

3.0

2.0 1.6

0.9 0.9 1.0 0.7 0.8 0.5 0.5 0.6 0.6 0.3 0.3 0.4 0.4 0.0 0.0 7.2 12.2 0.0 -0.1 0.0 -0.4 -0.6 -1.0 -0.7 -0.9 -0.8 -0.8 -1.0 -1.0 -1.2 -1.1 -1.4 -2.0

-2.4 -3.0

-4.0 KKJI6E SSDJFL XI4B45 DTDBJJ ZGZFSZ IPQ2PX RY77T7 KJEYDH C6JVZQ 7HJS9Q ZCNK6F Z6Z10Q 64XLPQ JAD7AR DTRRZK SKR23G AEEU0E 7CAH7X TSQPSQ 0KT0UD AGXHTY RBYOV1 SVVVQE DDIM3Y LQLGLM OGYYMJ CWRLNL POVZUG X328WA OBVQVP LVQGGU z-scores can be interpreted by participants in line with ISO 13528:2005, secion 7.4.2 and ISO/IEC guide43-1:1997(E) as follows: IzI < 2 = satisfactory 2 ≤ IzI ≤ 3 = questionable IzI > 3 = unsatisfactory According to the recommendations in ISO 13528:2005, an unsatisfactory z-score is considered to give an action signal and a questionable z- score is considered to give a warning signal. A single action signal or warning signal in two successive rounds shall be taken that an anomaly has occured that requires inverstigation.

47 Z-Score Report per Sample per Substance

Round: 2018/1 Substance: BS-3; 6-MAM Dispersion of z-scores using different analytical techniques for the quantification of 6-MAM in 2018/1 BS-3

0 Title

-2

-4

-6

-8 GC-MS LC-MS

-10 HPLC GC-FID GC-MS/LC-MS

48 Z-Score Report per Sample per Substance

Round: 2018/1 Substance: BS-3; Nordazepam Dispersion of z-scores using different analytical techniques for the quantification of Nordazepam in 2018/1 BS-3

0 Title

-2

-4

-6

-8 HPLC GC-ECD GC-MS LC-MS

-10 HPLC GC-FID GC-MS/LC-MS

49 INTERNATIONAL QUALITY ASSURANCE PROGRAMME (IQAP) INTERNATIONAL COLLABORATIVE EXERCISES (ICE)

Z-Scores for Test Sample 3

6-Monoacetylmorphine Nordazepam Deviation Deviation Code Concentration from Code Concentration from z-score z-score (ng/ml) robust (ng/ml) robust average average SVVVQE 16 -572 -2.9 C6JVZQ 30 -1840 -2.4 C6JVZQ 40 -548 -2.3 KKJI6E 814 -1056 -1.4 SKR23G 106 -482 -1.9 64XLPQ 1000 -870 -1.2 0KT0UD 206 -382 -1.6 KJEYDH 1004 -866 -1.1 KJEYDH 253 -335 -1.5 0KT0UD 1089 -781 -1.0 8BJ88Q 400 -188 -1.2 ZCNK6F 1138 -732 -1.0 SSDJFL 434 -154 -1.1 7CAH7X 1182 -688 -0.9 RBYOV1 470 -118 -1.0 Z6Z10Q 1250 -620 -0.8 JJVUJ4 494 -94 -0.7 RY77T7 1257 -613 -0.8 JAD7AR 501 -87 -0.7 SSDJFL 1350 -520 -0.7 OGYYMJ 522 -66 -0.7 OGYYMJ 1410 -460 -0.6 35XDDI 536 -52 -0.3 JAD7AR 1557 -313 -0.4 RY77T7 543 -45 -0.3 AEEU0E 1800 -70 -0.1 DTDBJJ 549 -39 -0.2 DTRRZK 1864 -6 0.0 LQLGLM 589 1 -0.2 DDIM3Y 1900 30 0.0 AGXHTY 605 17 0.0 DTDBJJ 1900 30 0.0 AEEU0E 607 19 0.1 LVQGGU 2107 237 0.3 IPQ2PX 618 30 0.1 LQLGLM 2111 241 0.3 ZGZFSZ 619 31 0.1 SKR23G 2182 312 0.4 TSQPSQ 625 37 0.2 OBVQVP 2186 316 0.4 XI4B45 637 49 0.2 7HJS9Q 2228 358 0.5 X328WA 666 78 0.2 X328WA 2267 397 0.5 64XLPQ 680 92 0.2 IPQ2PX 2296 426 0.6 70YAAL 688 100 0.3 XI4B45 2315 445 0.6 CWRLNL 713 125 0.4 TSQPSQ 2400 530 0.7 LVQGGU 722 134 0.5 AGXHTY 2458 588 0.8 POVZUG 804 216 0.6 ZGZFSZ 2573 703 0.9 OBVQVP 857 269 0.6 CWRLNL 2574 704 0.9 KKJI6E 987 399 0.7 POVZUG 3080 1210 1.6 Z6Z10Q 1156 568 1.0 RBYOV1 7306 5436 7.2 7HJS9Q 1261 673 1.6 SVVVQE 11070 9200 12.2

Sample 4 Analysis

Identified substances for Test Sample 4

Code Identified Substances 0KT0UD 6-MAM 11O1XT mephedrone 35XDDI Mephedrone 3UYPY3 Not detected 48QEE4 Methadone 4E7ZIJ - 64XLPQ mephedrone 6EEUE1 Mephedrone 7HJS9Q Mephedrone 7NUSSC No drug AGXHTY mephedrone (4-MMC) C6JVZQ None D6Q06A no drugs found. DXXYXX Mephedrone F9Q8GB none FXHPFX Mephedrone JJVUJ4 4-methylmethcathinone KHAFAU Mephedrone KKJI6E mephedrone KU9BHP No drugs LQLGLM Mephedrone M7F7FP none MMMMG5 mephedrone OBVQVP Mephedrone PI4IFI None POVZUG Mephedrone PXMPP5 MEPHEDRONE Q38299 MEPHEDRONE Q4CEQC mephedrone QAHFEE Benzoylecgonine QQQQNH 4-Methylmethcathinone (Mephedrone) and Methcathinone RBYOV1 none RSAONM Mephedrone SJFHU7 NO FOUND ABUSE DRUGS SKR23G Mephedrone TSQPSQ Mephedrone UUZZZU monoacetyl morphine VYUQPU Mephedrone X328WA mephedrone XI4B45 Mephedrone

Statement of findings for Test Sample 4

Code Mephedrone 0KT0UD -

0VDD9G ANP

11O1XT + It indicates the intake of mephedrone 220U22 - The presence of drugs or psychotropic drugs was not detected in the analyzed sample. 35XDDI + Mephedrone - Detected 3BSMFK -

3UYPY3 ANP It was not detected the searched substances according the results. 48QEE4 - general extraction, identification with HPLC/DAD and confirmation by GC/MS 4E7ZIJ ANP - 5I5O5B +

64XLPQ +

6EEUE1 +

70YAAL ANP Sample tested negative for Enzyme immunoassay screening for Drugs of abuse, no confirmation tests needed. 7CAH7X -

7GH9UT ANP

7HJS9Q + The simple BS-3 contains TRACES of MEPHEDRONE 7NUSSC - No drugs have been found 8BJ88Q - sample negative 8CHL4D ANP

99LN9D - No common drugs were detected in sample 2018/1/BS-4. 9D99UW ANP The sample 2018/1/BS-4 was analyzed for benzodiazepines, cocaine, amfetamines GHB/GBL and do not found to contain the drugs ot those groups. 9NRNMD ANP

Code Mephedrone A3V9ZR -

A9WZZV -

AEEU0E +

AGXHTY + Mephedrone, also known as 4-methyl methcathinone (4-MMC) or 4-methyl ephedrone, is a synthetic stimulant drug of the amphetamine and cathinone classes.Users have reported that mephedrone causes euphoria, stimulation, an enhanced appreciation for music, an elevated mood, decreased hostility, improved mental function and mild sexual stimulation; these effects are similar to the effects of cocaine, amphetamines and MDMA, and last different amounts of time depending on the way the drug is taken. C6JVZQ - Caffeine and Theobromine CWRLNL +

CYQZSY ANP

D6Q06A - caffeine. DDDDB7 -

DDIM3Y ANP

DTDBJJ ANP Test sample 2018/1/BS-4 does not contain controlled drugs therefore Negative for Screening and Confirmatory analyses. DTRRZK ANP

DXXYXX + In sample BS-4 the drug Mephedrone was found EMMMOU ANP Common drugs not detected. EQUPXX - The substances that were tested for weren´t found to be present in the sample analysed. F9Q8GB - - FXHPFX + Mephedrone is a synthetic stimulant in the amphetamine and cathinone class. Mephedrone is a Schedule I substance in the United States.

FXQFEB ANP

GK5SOG ANP

HKEKZQ -

HTTTKJ -

Code Mephedrone IMDPB5 ANP Drugs not detected. IPQ2PX - Sample contains no substances from ICE menu JAD7AR ANP Analyzed drugs were not detected JJVUJ4 + 4-methylmethcathinone K0UCFK ANP

K2222R ANP

KHAFAU + Prior ingestion of Mephedrone KJEYDH ANP

KKJI6E + positive KU9BHP ANP The sample SM4 does not contain any substance from ICE menu. LQLGLM + The sample was found to contain mephedrone, which is a designer drug (synthetic cathinone) with stimulating effects. LVQGGU -

M7F7FP - We found only caffein. MDDHDD - Normal MMMMG5 + Sample 2018/1/BS-4 contain mephedrone. OBVQVP + Mephedrone use. OGYYMJ -

OQOODA -

PI4IFI ANP Sample 2018/1/BS-4 found not to contain any drugs POVZUG + Presence of mephedrone (4-MMC) PXMPP5 + IN THE SAMPLE BS-4 WAS FOUND MEPHEDRONE Q38299 +

Q4CEQC +

Code Mephedrone QAHFEE -

QQQQNH + free QSQIQY ANP No drugs detected in BS4 sample. RBYOV1 - blank sample RSAONM + Positive to mephedrone. RY77T7 -

S06SXR ANP

S6LL6A ANP

SJFHU7 ANP IN THE SAMPLE NO FOUND DRUGS SKR23G + Methcatinone and mephedrone were detected in BS-4, 2018/1 exercise. SSDJFL ANP

SVVVQE -

TSQPSQ + - U7TYIH ANP Se relalizo prueba de orientacion (cod.110) para AMP/COC/THC; B20/TCA/BAR; MET/MOP; MDMA/MTD; con resultato negative para todos UUZZZU ANP

VJVDSU - Toxicological examination yielded negative result VRRGOL +

VYUQPU + we found Mephedrone as psychotropic substances WWYBNT ANP

X328WA +

XI4B45 + This person consumed mephedrone. Z6Z10Q -

ZCNK6F -

Code Mephedrone ZGZFSZ -

ZNZZSU -

Identification methods for Test Sample 4

Legend: S ... used for Screening I ... used for Identification SI ... used for both

RESPONSE SUMMARY FOR TEST SAMPLE 4

Participants: 91

The response summary of all 91 participating laboratories for the identification of BS-4, frequency of use of screening and identification techniques and false positives and negatives:

Identification of Test Sample-4:

Substance Name Number of laboratories correctly identifying: Mephedrone 29

False positives for Test Sample-4:

Round Code: Substance Name: Tech Code: 0KT0UD 6-Monoacetylmorphine 231 48QEE4 Methadone 161/180 QAHFEE Benzoylecgonine 150 QQQQNH Methcathinone 231 UUZZZU Monoacetylmorphine 180 SKR23G Methcathinone 180/231

False negatives for Test Sample-4 Round Answer Tech Round Answer Tech Code: Code: Code: Code: Code: Code: ZGZFSZ - 210 MDDHDD - 180 RY77T7 - 230 VJVDSU - 180 OGYYMJ - 231 48QEE4 - 161/180 QAHFEE - 150 7NUSSC - 161/180 C6JVZQ - 180 D6Q06A - 180/231 99LN9D - 180 IPQ2PX - 180 SVVVQE - 180 M7F7FP - 150 8BJ88Q - 231 A3V9ZR - 180 LVQGGU - 180 DDDDB7 - 150/180 A9WZZV - 180/231 HKEKZQ - 180 RBYOV1 - 180 OQOODA - 180 0KT0UD - 231 ZNZZSU - 150 ZCNK6F - 180 F9Q8GB - 231 EQUPXX - 180 3BSMFK - 180 Z6Z10Q - 231 HTTTKJ - 180 220U22 - 120 7CAH7X - 180

The following thirty laboratories did not carry out analysis for mephedrone in test sample 4:UUZZZU, S06SXR, DTDBJJ, WWYBNT, CYQZSY, 8CHL4D, KJEYDH, JAD7AR, SJFHU7, 9NRNMD,7GH9UT,, U7TYIH, 9D99UW, 4E7ZIJ, 3UYPY3, KU9BHP, DTRRZK, IMDPB5, PI4IFI, 70YAAL, DDIM3Y, K0UCFK, SSDJFL, K2222R, FXQFEB, 0VDD9G, GK5SOG, QSQIQY, S6LL6A and EMMMOU

Frequency of use of screening, identification and quantification techniques:

Response Summary Participants 91 Technique 100 110 120 141 150 160 161 170 172 180 210 230 231 Screening (No.) 1 54 2 1 2 0 0 0 0 20 9 3 11

(%) 1.1 60.0 2.2 1.1 2.2 0.0 0.0 0.0 0.0 22.2 10.0 3.3 12.2

Identification (No.) 0 3 1 0 8 0 9 1 1 67 5 6 30 (%) 0.0 3.3 1.1 0.0 8.9 0.0 9.9 1.1 1.1 74.4 5.6 6.7 33.3

Quantification (No.) 0 0 0 0 0 1 2 0 1 24 2 2 17 (%) 0.0 0.0 0.0 0.0 0.0 602.6 5.1 0.0 2.6 61.5 5.1 5.1 43.6 Z-Score Report per Sample per Substance

Round: 2018/1 Robust average = 61 ng/ml Substance: BS-4; Mephedrone UNODC value = 86 ng/ml

4.0

3.0

2.0

1.0 0.5

0.1 10.3 26.4 34.8 0.0 -0.1 -0.4 -0.5 -0.5 -1.0

-1.3

-2.0 -1.6

-3.0

-4.0 KKJI6E 64XLPQ AEEU0E Q38299 TSQPSQ AGXHTY LQLGLM CWRLNL POVZUG X328WA OBVQVP

61 Z-Score Report per Sample per Substance

Round: 2018/1 Substance: BS-4; Mephedrone Dispersion of z-scores using different analytical techniques for the quantification of Mephedrone in 2018/1 BS-4

10.0

8.0

6.0

4.0

2.0

0.0 Title

-2.0

-4.0

-6.0 HPLC GC-MS LC-MS -8.0

-10.0 HPLC GC-FID GC-MS/LC-MS

62 INTERNATIONAL QUALITY ASSURANCE PROGRAMME (IQAP) INTERNATIONAL COLLABORATIVE EXERCISES (ICE)

Z-Scores for Test Sample 4

Mephedrone Code Deviation from Concentration (ng/ml) z-score robust average AEEU0E 9.5 -52 -1.6 Q38299 22 -39 -1.3 64XLPQ 46 -15 -0.5 CWRLNL 47 -14 -0.5 TSQPSQ 50 -11 -0.4 OBVQVP 59 -2 -0.1 AGXHTY 64 3 0.1 LQLGLM 76 15 0.5 KKJI6E 387 326 10.3 X328WA 895 834 26.4 POVZUG 1160 1099 34.8

The Laboratory and Scientific Section UNODC, International Centre Wagramer Strasse 5, P.O. Box 500 A-1400, Vienna, AUSTRIA Email: [email protected]