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UNITED NATIONS INTERNATIONAL CONTROL PROGRAMME

SCIENTIFIC AND TECHNICAL NOTES SCITEC/13 December 1996

Studies on Colour Tests for Field Detection of Narcotic and Psychotropic Substances under International Control (No. II)

Screening Colour Test and Specific Colour Test for the Detection of Non- and and

Keizo Watanabe

prepared by

LABORATORY SECTION TECHNICAL SERVICES BRANCH

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Table of Contents

Purpose of this note...... 2

Manufacture and international control 2

Medical use 3

Chemical identification 6

Synthesis 7

Colour test 9

Experimental 10

Results and discussion ...... 14

References...... 23

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Purpose of this note

1. In view of the increasing interest expressed by Member States in the possibility of identifying methaqualone and mecloqualone by means of a simple colour reaction, a study was carried out to explore such a possibility at the UNDCP laboratory. This note summarizes the results of that study.

Manufacture and international control (1,2)

2. In 1972, methaqualone emerged as a major drug of non-medical use in the United States and subject of widespread publicity and public concern. It also had a similar history in other countries, particularly in Great Britain, Germany and . Methaqualone was first synthesized in 1951 and introduced in Europe in 1956. In 1959, it was introduced in Great Britain and marketed as Melsedin in 150 mg tablets by the Boots Pure Drug Company. This preparation was never widely prescribed.

3. Methaqualone was introduced to the former West Germany in 1960, marketed by Merck as Revonal in 200 and 300 mg tablets. Two years later, the drug became available in the former East Germany, marketed under the trade name Dormutil. In both East and West Germany, methaqualone was sold over the counter, unlike which required a prescription, and quickly became widely used and abused, particularly by young people. In the decade following methaqualone's introduction into the world market, it became a drug of non-medical use in France, Italy, Sweden, Argentina, Norway, Ireland and . Overdose from methaqualone was considered to be a serious problem.

4. Methaqualone was introduced to Japan in October 1960 by the Eisai Company and marketed under the trade name Hyminal. Freely available without prescription, methaqualone was widely used for non-medical purposes.

5. In 1965, Roussel introduced a combination tablet, Mandrax, which contained 250 mg of methaqualone base and 25 mg of hydrochloride. Mandrax rapidly achieved a considerable popularity and a survey in 1968 showed that it was the most commonly used , accounting for 30 of all hypnotic prescriptions. Other preparations were marketed, but none reached equal popularity. It is surprising that Mandrax, a methaqualone preparation marketed six years after the first methaqualone containing product, became so much more widely used. It is claimed that this is because methaqualone together with diphenhydramine is a more efficient hypnotic. The apparent effect of diphenhydramine in promoting the absorption and increasing the peak plasma methaqualone concentration can be seen in comparative studies on Melsedin versus Mandrax.

6. The major episodes of methaqualone misuse and the most fully documented, occurred in Great Britain, Germany and Japan. Until 1973, however, federal officials in the United States did not give much weight to the foreign reports on methaqualone misuse and dependence liability. The warning statement to doctors accompanying methaqualone products, approved by the FDA in 1967 and unchanged until the imposition of Schedule II control in 1973, stated only that "psychological dependence has been rarely reported; physical dependence has not clearly been demonstrated". Despite the British, German and Japanese reports available at that time, in 1967, the FDA approved the marketing of a new 300 mg methaqualone preparation, Quaalude.

7. A review of the foreign experience with methaqualone misuse reveals certain pattern which were

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later repeated in the United States. First, methaqualone was widely marketed as a new, safe hypnotic superior to the barbiturates and other traditional sleeping medications. Secondly, it was readily accepted both by physicians and by the drug-using public because of its particular pharmacological properties, its free availability and its reputation for producing a pleasant, allegedly safe euphoria. As a result, methaqualone rapidly developed a following among recreational drug users. Thirdly, as methaqualone emerged as a high frequency drug of misuse, reports regarding its toxicity, its tolerance potential, and its dependence liability became more numerous.

8. In its 1964 report, the World Health Organization Expert Committee on Addiction Producing Drugs noted the "epidemic-like outbreak of abuse of hypnotic drugs in a particular region. Methaqualone is reported to constitute about 4/5 of the total amount of hypnotic drugs abuse in the group studied."(5) In 1979, the Commission on Narcotic Drugs decided to place methaqualone under international control, initially in Schedule IV and later transferred it to Schedule II of the 1971 Convention on Psychotropic Substances.

9. No diversion of substances included in Schedule II of the 1971 Convention from the licit manufacture and trade into the illicit channels has been identified since l990. However, although diversion of methaqualone last occurred in 1988, attempts at diversion of this substance has continued, mainly through the use of falsified import authorizations. Indeed, in summer 1991, a Swiss trading company approached a company in India in order to obtain 10 million tablets containing 400 mg of methaqualone and 40 mg of diphenhydramine hydrochloride each. When requested by the Indian company for the export permit, the Indian authorities informed the United Nations International Narcotics Control Board. Inquiry with the Swiss authorities revealed that the Swiss company interested in the purchase of methaqualone was not licensed to deal in pharmaceuticals and had never applied for the import permit. Investigations of the case continue in Switzerland.(6)

10. Only a few countries in Europe, namely Belgium, Spain and Switzerland, continue to use methaqualone in significant quantities for medical purposes. In recent years, the medical needs for methaqualone in those countries have been satisfied by using stocks in Switzerland or, occasionally, through manufacturing the substance in the Czech Republic (214 kg in 1994).(8) Mecloqualone has not been manufactured since 1980. Portugal, the only country that had reported having small stocks of the substance, exhausted those stocks in 1993.

11. Two international meetings took place recently on the subject of illicit traffic in methaqualone: 1) International Conference on the Illicit Traffic in Methaqualone between the Indian Sub-Continent and the East/Southern Region of Africa, organized by ICPO/Interpol, New Delhi, India, from 9 to 11 December 1992, and 2) Regional Seminar on Methaqualone, organized by UNDCP, Nairobi, Kenya, from 18 to 20 January 1993.(7)

Medical use

(I) Methaqualone

12. Methaqualone is a non-barbiturate sedative-hypnotic agent of the quinazoline group, used to produce sleep and daytime sedation in doses ranging from 150mg to 400mg.(9)(10)(11) Methaqualone is a central nervous system , effective for sedation at dosage ranges of 75 mg four times daily. Onset of sedative-hypnotic action occurs within 30 min. of ingestion and lasts between 6 to 8 hours. (1)

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13. Virtually insoluble in water, methaqualone is unsuitable for intravenous injection and is administered orally. Adverse physiological reactions to methaqualone include headache, hangover, menstrual disturbance, dryness of the mouth, nosebleed, dizziness, numbness, diarrhea and anorexia,(12) neurotoxic effects have been discussed (15). Absorption and plasma levels of methaqualone after oral administration to man have been studied.(13)

14. Studies on methaqualone's metabolism in man were reported in 1960, and in animals in 1963.(12)(13) Methaqualone was introduced pharmaceutically in 1959 for use as a non-addictive, non- barbiturate sleeping pill. Metabolite detection for forensic science purposes was reported in 1976.

14. Pharmacokinetic studies on methaqualone have shown a wide subject variation in the rate of absorption and a faster absorption rate for the hydrochloride salt than for the free base.(14) It is known that methaqualone is concentrated in body fat and brain and that it is metabolised at a rate which ensures 80 elimination in 24 hours. Methaqualone is readily absorbed from the gastrointestinal tract and metabolized almost entirely in the .(15) It is very rapidly and extensively metabolized in man via hydroxylation, so that very little unchanged drug, usually less than 5 , is excreted in urine.

16. Metabolic pathways involving formation of dihydroxy- and hydroxy-methoxy-derivatives exist. However, the major pathway is monohydroxylation at any one of ten possible sites (14). and the five most common monohydroxy metabolites in human urine are shown in Figure 1.

17. Methaqualone is particularly attractive to non-medical drug users because in certain settings it can produce euphoric effects. Nicknamed the "love drug", methaqualone has developed a widespread reputation among non-medical users as an aphrodisiac because it induces disinhibition and has been reported to produce paraesthetic effects or tingling sensations. Methaqualone is potentiated by other central nervous system depressant, such as barbiturates and , and it is frequently used for non- medical purposes in conjunction with these and other depressant drugs.(1)

CH3 - 5 - CH2OH

NN NN

CH2OH CH3 O O

Metabolite I Metabolite II

CH3 CH 3

NN NN OH

CH3 CH3 O O Metabolite III

Methaqualone

OH CH3 CH3

NN NN

CH3 CH3 O O

Metabolite IV Metabolite V

OH

I: 2-methyl-3-(o-hydroxymethylphenyl)-4(3H)- II: 2-hydroxymethyl-3-o-tolyl-4(3H)-quinazolinone III: 2-methyl-3-(o-methyl-m-hydroxyphenyl)-4(3H)-quinazolinone IV: 2-methyl-3-(o-methyl-p-hydroxyphenyl)-4(3H)-quinazolinone V: 2-methyl-3-o-tolyl-6-hydroxy-4(3H)-quinazolinone

Figure 1. Methaqualone and its monohydroxy metabolites

(II) Mecloqualone

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18. Mecloqualone was first prepared in 1960 and studies on its metabolism in man were reported in

N CH3 N CH3

N N

O O H3C Cl

1974.(12) Chemical identification

19. Methaqualone, 2-methyl-3-o-tolyl-4(3H)-quinazolinone, was introduced as a non-barbiturate hypnotic of the quinazoline group, to which also mecloqualone, 2-methyl-3-(o-chlorophenyl)-4(3H)- quinazolinone, belongs.(15)

Methaqualone Mecloqualone

Figure 2. Chemical structures of methaqualone and mecloqualone

(I) Methaqualone

base:

general formula: C16H14N2O molecular weight: 250.29 elementary composition: C 76.78 ; H 5.64 ; N 11.19 ; O 6.39 melting point: 120°C; also given as 114-116°C Soluble in ethanol, ether, . Practically insoluble in water.

hydrochloride:

general formula: C16H14N2O ⋅ HCl molecular weight: 286.76 melting point: 255-265°C Soluble in ethanol, ether. Practically insoluble in water.

(II) Mecloqualone

base:

general formula: C15H11ClN2O

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molecular weight: 270.74 elementary composition: C 66.55 , H 4.10 , Cl 13.10 , N 10.35 , O 5.90 melting point: 126-128°C

hydrochloride:

general formula: C15H11ClN2O ⋅ HCl molecular weight: 307.21 melting point: 239-241°C

NH2 H N CH3 Cl N CH3 O 3+3 + PCl3 H3PO3 + 3 HCl + 3 H2O + 3 OH N O O Cl

Synthesis

(I) Methaqualone

20. N-acetylanthranilic acid is cyclized through condensation with o-toluidine in the presence of phosphoryl chloride, and then the mixture is rendered alkaline to precipitate the crude product. Purification of the crude product is carried out via recrystallization from isopropanol and methaqualone hydrochloride is made by combination with an equimolar quantity of hydrochloric acid.

(II) Mecloqualone (16)(17)(18)

21. Synthesis of mecloqualone is conducted according to a general method described by Grimmel et al. (Figure 3.).

Mecloqualone

Figure 3. Synthesis of mecloqualone

22. Two basic methods for the clandestine manufacture of either methaqualone or mecloqualone have been encountered. The first method is a two-step reaction that involves the preparation of N-acetylanthranilic acid from anthranilic acid and acetic anhydride followed by condensation with either

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o-toluidine to produce CH3 methaqualone or with o- chloroaniline to produce N mecloqualone. Phosphorus trichloride is used to remove water produced in the reaction.(13)(19) N R3

23. The second method is carried out in a one-step O R1 R2 reaction by refluxing anthranilic acid, o-toluidine (o-chloroaniline, respectively) and acetic acid or acetic anhydride. Polyphosphoric acid may be added to remove water. Purification is accomplished by dissolving the solid residue in and precipitating the hydrochloride salt from a methanol- solution.(13) Possible by-products could be o-methyl , o-chloroacetanilide and 2-methyl-3-o-carboxyphenyl- 4-quinazolinone. The reported synthetic routes for are not complicated and involve one or two-step procedures that can be adapted to clandestine laboratory processes without difficulty. Recently, another method of clandestine methaqualone/mecloqualone synthesis was encountered in which isatoic anhydride is condensated with o-toluidine (o-chloroaniline, respectively) and acetic anhydride or acetylacetone.

24. Nitromethaqualone, another representative of the quinazolinone group, was synthesized following the former East Germany Patents 31,039 and 35,123.(20)

methaqualone: 2-methyl-3-o-tolyl-4(3H)-quinazolinone mecloqualone: 2-methyl-3-(o-chlorophenyl)-4(3H)-quinazolinone nitromethaqualone: 2-methyl-3-(o-methoxy-p-nitrophenyl)-4(3H)-quinazolinone

The chemical structures together with the common and trade names are listed in Figure 4. and Table 1.

Figure 4. Chemical structure of quinazolinone series

Table I. Chemical structures, common and trade names for methaqualone mecloqualone and nitromethaqualone

Common name R1 R2 R3 Trade name

methaqualone CH3 H H Revonal, Mandrax

mecloqualone Cl H H Nubarene

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nitromethaqualone OCH3 H NO2 Pamox

25. Compounds I to XVI (Figure 5. and Table II.) were synthesized by reacting a solution of aniline, or the appropriate substituted aniline, with N-acetylanthranilic acid in the presence of phosphorous trichloride.(12)

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Table II. Chemical structures and chemical names for methaqualone-related compounds

No. R1 R2 R3 Chemical name

I H H H 2-methyl-3-phenyl-4-quinazolinone

* II CH3 H H 2-methyl-3-o-tolyl-4(3H)-quinazolinone

III H CH3 H 2-methyl-3-m-tolyl-4(3H)-quinazolinone

IV H H CH3 2-methyl-3-p-tolyl-4(3H)-quinazolinone

V F H H 2-methyl-3-o-fluorophenyl-4-quinazolinone

VI H F H 2-methyl-3-m-fluorophenyl-4-quinazolinone

VII H H F 2-methyl-3-p-fluoromethyl-4-quinazolinone

VIII Cl H H 2-methyl-3-o-chlorophenyl-4-quinazolinone**

IX H Cl H 2-methyl-3-m-chlorophenyl-4-quinazolinone

X H H Cl 2-methyl-3-p-chlorophenyl-4-quinazolinone

XI Br H H 2-methyl-3-o-bromophenyl-4-quinazolinone

XII H Br H 2-methyl-3-m-bromophenyl-4-quinazolinone

XIII H H Br 2-methyl-3-p-bromophenyl-4-quinazolinone

XIV I H H 2-methyl-3-o-iodophenyl-4-quinqzolinone

XV H I H 2-methyl-3-m-iodophenyl-4-quinazolinone

XVI H H I 2-methyl-3-p-iodophenyl-4-quinazolinone

* = methaqualone ** = mecloqualone

Colour test

26. Sodium-bismuth iodide (modified Dragendorff's reagent) is being employed as a chromogenic agent for a number of compounds containing a basic atom. Hence, it was thought worthwhile to examine the utility of this reagent to produce an orange colour complex with methaqualone in the presence of a saturated solution of ammonium vanadate.(21) Three colour tests for the presumptive identification of methaqualone and mecloqualone have been reported: 1) Cobalt thiocyanate test(22,23,24), 2) Medina-Goldston test(25,26,27,28), 3) Fischer-Morris test(29).

27. An improved test for methaqualone with a modified cobalt(II) thiocyanate reagent was reported. With regard to the Cobalt thiocyanate test, it is well known that many other materials, some harmless and not controlled by national legislations or international treaties such as diphenylamine and controlled

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substances such as , and may give similar colours with the test reagents. The traditional colour test for methaqualone and mecloqualone - as well as for cocaine - consists of the addition of a cobalt(II) thiocyanate solution to give a blue flaky precipitate. Since Young's first report(30), there have been no important modifications to this test.

28. Fischer-Morris test was developed as a simple and reliable screening test for methaqualone, and diphenhydramine, two substances which are commonly encountered with or in place of methaqualone.

29. Medina and Goldston developed a simple and easy to interpret colour test based on the reaction of methaqualone at the N=C bond to form an amine product which condenses with p-dimethylaminocinnamaldehyde. The test will detect methaqualone down to 0.5 mg. Two drops of 0.5 M sodium borohydride reagent are added to a small amount of sample placed in a test tube and let stand with 15-20 drops of 0.1 p-dimethylaminocinnamaldehyde (p-DMACA) reagent. The appearance of a pink colour indicates the presence of methaqualone.

30. Methaqualone is partially reduced to its corresponding tetrahydroquinazoline by sodium borohydride. The condensation of the reduced product with p-DMACA gives a pink colour which darkens on standing. The increased intensity of the colour suggests that reduction continues until the sodium borohydride is consumed. Mecloqualone produces the same colour as methaqualone. Amongst the fifty-four other drugs tested, the primary and secondary aromatic amine drugs, such as , procaine and tetracaine exhibited colour on contact with p-DMACA reagent. Some compounds formed a colour which progressed slowly (5-10 minutes) in intensity on standing.

31. In searching for a field test for methaqualone and mecloqualone for use by non-technical personnel, it is obvious a priori that no single reagent could be specific, but it was hoped that response to the test could be restricted to these abused drugs and possibly to a limited number of rarely encountered licit preparations.

Experimental

32. UNDCP laboratory was advanced to develop a reliable colour test for methaqualone and mecloqualone. Efforts were given a clear indication of presence of methaqualone and mecloqualone.

33. Several chemicals as well as several solvents were evaluated as candidate reagents for possible colour tests (Tables III. - VI.).

Table III. Canditate reagents (aldehyde type)

No. Reagent (aldehyde)

1 3-Acetoxy-4-hydroxybenzaldehyde

2 Anisaldehyde

3 Caprylaldehyde

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Table III. Canditate reagents (aldehyde type)

No. Reagent (aldehyde) 3 Cinnamaldehyde

5 2,3-Dimethoxybenzaldehyde

6 3,4-Dimethoxybenzaldehyde

7 p-Dimethylaminocinnamaldehyde

8 4-Dimethylaminobenzaldehyde

9 m-Hydroxybenzaldehyde

10 Pelargonaldehyde

11 Salicylaldehyde

Table IV. Candidate reagents (organic solvent type)

No. Reagent (solvent)

1 Acetonitrile

2 n-Butanol

3 Carbon tetrachloride

4 Dimethylformamide (DMF)

5 Dioxane

6 Ethanol

7 Glycerine

8 n-Hexane

9 Methanol

10 n-Propanol

11 iso-Propanol

12 Propylene glycol

13 Propylene glycol + lithium hydroxide

14 Tetrahydrofuran (THF)

Table V. Candidate reagents (alkali type)

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No. Chemical Name

1 Sodium borohydride NaBH4

2 Sodium borohydride/Sodium sulfate NaBH4/Na2SO4

3 Lithium borohydride LiBH4

4 Lithium borohydride/Sodium sulfate LiBH4/Na2SO4

Table VI. Candidate reagents (acid type)

No. Chemical Name Chemical Formula

1 Acetic acid CH3COOH

2 Formic acid HCOOH

3 Hydrocloric acid HCl

4 Nitric acid HNO3

5 Phosphoric acid H3PO4

6 Sulfuric acid H2SO4

34. p-Dimethylaminocinnamaldehyde together with dimethylforamide (DMF) were selected as candidate colour reagents for methaqualone and related compounds. Sodium borohydride and formic acid were also selected as candidate colour reagents for this colour test. (Table VII., Test Flow Chart)

Test Flow Chart

METHAQUALONE / MECLOQUALONE

+

2.5 p-Dimethylaminocinnamaldehyde in dimethylformamide

+

5 Sodium borohydride in sodium sulfate

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+

98-99 Formic acid

+

Fluorescence reaction: UV lamp at 366 nm

Table VII. Reagent composition

Reagent Substance

A 2.5 p-dimethylaminocinnamaldehyde in dimethylformamide

B 1g sodium borohydride mixed with 20g sodium sulfate

C 98-99 formic acid

34. Carrying out discriminatory (cross reactivity) testing on methaqualone and mecloqualone, the specific colour test was improved and is described as follows:

Step I: 1) Place a small amount of the suspected material on a spot plate. 2) Add three drops of reagent A. 3) Add 1/2 the size of a match tip of reagent B. 4) Add three drops of reagent C.

Result (I): Reddish-pink colour indicates the possible presence of methaqualone or mecloqualone.

Step II: 5) Transfer a small amount of the product obtained with Step I to another cavity of the spot plate. 6) Add three drops of reagent C. 7) Observe fluorescence under a UV lamp at 366 nm.

Result (II): Brilliant green fluorescence indicates the possible presence of methaqualone or mecloqualone.

Table VIII. Substance classes/number of substances tested for cross-reactivity

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No. Substance class Number of substances tested

1 Mecloqualone and Methaqualone 9 samples

2 alkaloids 14

3 alkaloids 8

4 Amfetamines 20

5 Barbiturates 10

6 Benzodiazepines 32

7 Other substances under int. control 8

8 Other substances not under int. control 118

Total number of substances tested 219

Results and discussion

36. Some chemicals have been examined as candidate reagents (Tables III. - VI.). p-Dimethylaminocinnamaldehyde (p-DMACA), dimethylformamide, sodium borohydride and formic acid have been selected for methaqualone and mecloqualone (Tables VII.).

37. Amongst the several solvents examined for suitability for the test, dimethylformamide is recommended as the solvent for p-dimethylaminocinnamaldehyde (p-DMACA). Optimum reagent concentration for p-DMACA was found to be 2.5 . Since sodium borohydride is moisture sensitive, it is mixed with anhydrous sodium sulfate. This reagent should be freshly prepared. The possibility for alternative reagents to sodium borohydride/sodium sulfate will be dealt with in future studies.

38. Methaqualone reference sample yielded the same result with the described test as illicit preparations of the substance.

39. The colour reaction examined in this study was also tested on about 220 chemical substances for possible cross-reactivity (Tables IX. - XVI.). The results obtained were encouraging and seemed to justify a preliminary report from UNDCP, even though time did not permit for the reaction to be exhaustively tested.

40. Some substances controlled and not controlled by national legislations or international treaties gave similar colours after Step I, but none of them yielded the same fluorescence colour as methaqualone with Step II. In addition, these fluorescence colours were found to be stable for more than three months.

41. The reaction mixtures with other drugs which did not form distinct colour complexes either remained clear or showed very faint colours which were considered as negative results.

42. The test is simple and rapid, and provides results that can be easily interpreted by chemists and non-chemists. Furthermore, the test may be useful for detecting benzodiazepines. This will be the

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subject of a future study.

43. Methaqualone and mecloqualone can be detected, but cannot be distinguished from each other using p-dimethylaminocinnamaldehyde, sodium borohydride and formic acid.

44. The advantages of the selected test are specificity, simplicity, rapidity and ease of reproducibility, requiring only very small amounts of sample and chemicals and no special laboratory equipment.

Table IX. Mecloqualone and Methaqualone

No. Substance Result Step I Result Step II

1 Mecloqualone reddish Pink brilliant Green

2 Methaqualone reddish Pink brilliant Green

3 Methaqualone HCl reddish Pink brilliant Green

4 Methaqualone (illicit) UNX 1028/6 reddish Pink brilliant Green

5 Methaqualone (illicit) UNX 1028/11 reddish Pink brilliant Green

6 Methaqualone (illicit) UNX 1028/14 reddish Pink brilliant Green

7 Methaqualone (illicit) UNX 1028/19 reddish Pink brilliant Green

8 Methaqualone (illicit) UNX 1028/40 reddish Pink brilliant Green

9 Methaqualone tablet "Slipy" reddish Pink brilliant Green

Table X. Opium alkaloids

No. Substance Result Step I Result Step II

1 Acetylcodeine HCl (-)* (-)

* (-) = no reaction

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Table X. Opium alkaloids 2 (-) (-)

3 Codeine phosphate (-) (-)

4 (Diacetylmorphine) HCl (-) (-)

5 Heroin (illicit) UNH 196 (-) (-)

6 Heroin (illicit) UNH 206 (-) (-)

7 6-Monoacetylmorphine HCl (-) (-)

8 (-) (-)

9 Morphine HCl (-) (-)

10 Narcotine (-) (-)

11 Opium (-) (-)

12 Papaverine (-) (-)

13 Papaverine HBr (-) (-)

14 Thebaine (-) (-)

Table XI. Coca alkaloids

No. Substance Result Step I Result Step II

1 Cocaine (-) (-)

2 Cocaine (illicit) UNX 347 (-) (-)

3 Cocaine (illicit) UNX 799 (-) (-)

4 Cocaine (illicit) UNX 800 (-) (-)

5 Cocaine HCl (-) (-)

6 Crack (cocaine base illicit) (-) (-)

7 Ecgonine benzoylester (-) (-)

8 Ecgonine methylester (-) (-)

Table XII. Amfetamine and related compounds

No. Substance Result Step I Result Step II

1 Amfetamine sulfate (-) (-)

2 Amfetamine (illicit) UNX 704 (-) (-)

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Table XII. Amfetamine and related compounds

4 HCl (-) (-)

5 HCl (-) (-)

6 N,N-Dimethylamfetamine (-) (-)

7 HCl (-) (-)

8 HCl (-) (-)

9 Fenetylline HCl (-) (-)

10 HCl (-) (-)

11 Metamfetamine (-) (-)

12 Metamfetamine HCl (-) (-)

13 Metamfetamine (illicit) UNX 898 (-) (-)

14 HCl (-) (-)

15 (-) (-)

16 Norephedrine orangish Yellow (-)

17 (-) (-)

18 Phenylacetic acid (-) (-)

19 (-) (-)

20 Tenamfetamine HCl (-) (-)

Table XIII. Barbiturates

No. Substance Result Step I Result Step II

1 (-) (-)

2 (-) (-)

3 (-) (-)

4 (-) (-)

5 (-) (-)

6 (-) (-)

7 (-) (-)

8 (-) (-)

9 (-) (-)

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10 (-) (-)

XIV. Benzodiazepines

No. Substance Result Step I Result Step II

1 v. Reddish Orange (-)

2 v. Reddish Orange (-)

3 v. Reddish Orange (-)

4 Chlordiazepoxide v. Reddish Orange (-)

5 s. Reddish Brown (-)

6 v. Reddish Orange (-)

7 v. Reddish Orange (-)

8 v. Reddish Orange (-)

9 v. Reddish Orange (-)

10 Diazepam v. Reddish Orange (-)

11 v. Reddish Orange (-)

12 v. Reddish Orange (-)

13 v. Reddish Orange (-)

14 v. Reddish Orange (-)

15 v. Reddish Orange (-)

16 v. Reddish Orange (-)

17 v. Reddish Orange (-)

18 v. Reddish Orange (-)

19 v. Reddish Orange (-)

20 v. Reddish Orange (-)

21 v. Reddish Orange (-)

22 v. Reddish Orange (-)

23 v. Reddish Orange (-)

24 v. Reddish Orange (-)

25 v. Reddish Orange (-)

26 v. Reddish Orange (-)

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XIV. Benzodiazepines

No. Substance Result Step I Result Step II

27 v. Reddish Orange (-)

28 v. Reddish Orange (-)

29 v. Reddish Orange (-)

30 v. Reddish Orange (-)

31 v. Reddish Orange (-)

32 v. Reddish Orange (-)

Table XV. Other substances under international control

No. Substance Result Step I Result Step II

1 (-) (-)

2 yellowish Orange (-)

3 (-) (-)

4 Methadone HCl (-) (-)

5 Norlevorphanol (-) (-)

6 (-) (-)

7 Phencyclidine HCl v. reddish Orange (-)

8 fumarate v. reddish Orange (-)

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Table XVI. Substances not under international control

No. Substance Result Step I Result Step II

1 Acetanilide (-) (-)

2 Acetoacetanilide (-) (-)

4 3-Acetoxy-4-hydroxybenzaldehyde (-) (-)

5 Acetylglycine (-) (-)

6 N-Acetyl-dl-methionine (-) (-)

7 Acetylsalicylic acid (-) (-)

8 l- (-) (-)

9 beta-Alanine (-) (-)

10 p-Aminoacetophenone Pink (-)

11 Amylocaine (-) (-)

12 p-Arbutin (-) (-)

13 HBr (-) (-)

14 l-Arginin monohydrate (-) (-)

15 Atropine (-) (-)

16 Azobenzene Orange (-)

17 (-) (-)

18 Benzidine (-) (-)

19 Benzidine sulfate (-) (-)

20 Benzocaine v. deep Pink (-)

21 Benzoic acid (-) (-)

22 Benzoin (-) (-)

23 Brucine (-) (-)

24 (-) (-)

25 Caffeine citrate (-) (-)

26 (-) (-)

27 Cannabinol (-) (-)

28 Cholesterine acetate (-) (-)

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Table XVI. Substances not under international control

No. Substance Result Step I Result Step II 29 hydrate (-) (-)

30 1-Chloro-2,4-dinitrobenzene v. Red (-)

31 Cinchonidine deep Pink v.l. Blue

32 Cinchonidine HCl deep Pink (-)

33 Cinchonine deep Pink (-)

34 Cinchonine HCl deep Pink (-)

35 Cinnamic acid (-) (-)

36 Cinnamic acid benzylester (-) (-)

37 Cocarboxylase (-) (-)

38 Cumarin (-) v.l. Blue

39 2,3-Dichloro-5,6-dicyano- (-) (-) 1,4-benzoquinone

40 2,4-Dinitrobenzene v. Red (-)

41 2,4-Dinitrofluorobenzene v. Red (-)

42 Diphenhydramine HCl deep Pink (-)

43 Diphenylcarbazide (-) (-)

44 1,3-Diphenylguanidine (-) (-)

® 45 Eumed orangish Yellow (-) (preparation containing caffeine, salacetamide, propyphenazone and antipyrine)

46 Fenozolone (-) (-)

47 Flavon (-) (-)

48 d-Fructose (-) (-)

49 d-Galactose (-) (-)

50 HCl (-) (-)

51 Glucuronic acid (-) (-)

52 l-Glutamic acid (-) (-)

53 l-Glutamine m. Olive Green (-)

- 23 -

Table XVI. Substances not under international control

No. Substance Result Step I Result Step II 54 Hexanitrodiphenylamine (-) (-)

55 Hippuric acid (-) (-)

56 l-Histidine (-) (-)

57 Homatropine (-) (-)

58 (-) (-)

59 Hydrazine HCl (-) (-)

60 Hydrazine 2HCl (-) (-)

61 Hydrazine sulfate strong purplish Red (-)

62 Hyoscyamine HCl (-) (-)

63 Lactose (-) (-)

64 Lauric acid (-) (-)

65 Maltose (-) (-)

66 d-Mandelic acid v. Orange Yellow (-)

67 d-Mannose (-) (-)

68 Meconic acid v. Orange (-)

69 Methylphenylglyoxime (-) (-)

70 Myristic acid (-) (-)

71 Naphthalene (-) (-)

72 Orange Yellow (-)

73 Nicotinic acid s. Orange Yellow (-)

74 m-Nitroacetanilide (-) (-)

75 p-Nitroacetanilide (-) (-)

76 p-Nitroaniline s. Reddish Purple (-)

77 p-Nitrophenol (-) (-)

78 4-Nitrophenylhydrazine v. Orange (-)

79 l-Noradrenaline HCl (-) (-)

80 Oxalic acid s. Orange Yellow (-)

81 Palmitic acid s. Orange Yellow (-)

- 24 -

Table XVI. Substances not under international control

No. Substance Result Step I Result Step II

82 d-Pantothenic acid s. Orange Yellow (-)

83 (-) (-)

84 Phenacyl chloride (-) (-)

85 Phenothiazine (-) (-)

86 Picric acid s. Reddish Brown (-)

87 Pilocarpine HCl (-) (-)

88 Procaine HCl (-) (-)

89 Propylamide (-) (-)

90 Pyridoxine HCl (-) (-)

91 Reserpine (-) (-)

92 Riboflavine (-) (-)

93 Sucrose (-) (-)

94 (-) (-)

95 Salicylanilide v. Orange (-)

96 HBr (-) (-)

97 Semicarbazide HCl (-) (-)

98 l-Sorbose (-) (-)

99 Starch (-) (-)

100 Stearic acid (-) (-)

101 Sulfaguanidine Red Orange (-) (vanishing)

102 Sulfanilamide deep Purplish Red (-)

103 Sulfanilic acid (-) (-)

104 Sulfonal (-) (-)

105 Tannic acid (-) (-)

106 d-Tartaric acid (-) (-)

107 Tetracaine (-) (-)

108 (-) (-)

- 25 -

Table XVI. Substances not under international control

No. Substance Result Step I Result Step II

109 (-) (-)

110 Tricarballylic acid (-) (-)

111 N,2,6-Trichloro-p-benzo- Brown/dark Green (-) quinoneimine Red

112 Trigonelline HCl (-) (-)

113 2,4,5-Trimethylaniline s. Reddish Orange (-)

114 l-Tryptophan (-) (-)

115 Tungstophosphoric acid (-) (-)

116 Vanillic acid v. Orange (-)

117 Vanillin (-) (-)

118 d-Xylose (-) (-)

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