hon p.

1 [100%]

YAKUGAKU ZASSHI 128(6) 981987 (2008) 2008 The Pharmaceutical Society of Japan

981

Articles

Part II TLC
()

Analytical Data of Designated Substances (Shitei-Yakubutsu) Controlled by the

Pharmaceutical Aairs Law in Japan, Part II: Color Test and TLC
Nahoko UCHIYAMA, Maiko KAWAMURA, Hiroyuki KAMAKURA,
Ruri KIKURA-HANAJIRI,and Yukihiro GODA
National Institute of Health Sciences (NIHS), 1181 Kamiyoga,
Setagaya-ku, Tokyo 1588501, Japan
(Received January 11, 2008; Accepted March 11, 2008)
Many psychotropic substances are readily available in Japan via the Internet. To avoid the spread of drug abuse,
some drugs have been controlled as designated substances (Shitei-Yakubutsu) in Japan since 2007 by the Pharmaceutical Aairs Law. Twenty-nine designated substances (classied as tryptamine, phenethylamine and piperazine types)
were analyzed using color tests and TLC. The color tests were examined with the Marquis, Ehrlich, Simon's, Liebermann-Burehard's, and Mandelin reagents. The color of b-carbonyl-methylenedioxyphenetylamines produced by the
Marquis reagent was yellow, and 4-halo-2,5-dimethoxy phenethylamines reacted with the Marquis reagent to a give deep
yellow-green and/or a deep green color. Although all designated substances of the tryptamine type reacted with the
Ehrlich reagent to give a brown color, only 1-(2,4,6-trimethoxyphenyl) propan-2-amine (TMA-6) among the
phenethylamines showed a red color on treatment with the reagent. However, 3,4,5-trimethoxy and 2,4,5-trimethoxy
isomers of TMA-6 were not colored with the reagent. Thus, TMA-6 could be distinguished from isomers using the
Ehrlich reagent. We also analyzed the designated substances with thin-layer chromatography developed with two dierent solvent conditions. All substances were detected by UV254 nm and an iodoplatinate reagent. These results suggest that
color tests and TLC, followed by GC-MS and LC-MS analyses, can be used for preliminary identication of designated
substances.
Key wordspsychotropic substance; color test; TLC; designated substance; shitei-yakubutsu; drug abuse

Part I 3)

GC-MS LC-MS

18

32

31 1 19 4

1 20 1 11

4)

TLC

GC-MS, LC-MS, TLC, IR

Salvinorin A

1,2)

29

GC-

MS LC-MS

e-mail: kikuranihs.go.jp

1.

hon p.2 [100%]

982

Vol. 128 (2008)

Part I
3)

Sal-

Fig. 1
2.

vinorin A 29

2C-B [ 2- ( 4-Bromo-2,5-dimethox-

p-dimethylaminobenzaldehyde 0.5 g

yphenyl)ethanamine], DOB[1-(4-Bromo-2,5-dime-

32 50 ml

thoxyphenyl ) propan-2-amine ] ,

2C-T-7 [ 2- ( 2,5-Di-

5,6)

methoxyphenyl-4-propylsulfanyl-)ethanamine], DMA

0.05 g 10 ml

[1-(2,5-Dimethoxyphenyl)propan-2-amine],

DOM

1 g

[1-(2,5-Dimethoxy-4-methylphenyl)propan-2-amine],

10 ml 5)

DOET[1-(2,5-Dimethoxy-4-ethylphenyl)propan-2-a-

mine], TMA[1-(3,4,5-Trimethoxyphenyl)propan-2amine ] ,

TMA-2 [ 1- ( 2,4,5-Trimethoxyphenyl ) pro-

pan-2-amine ] ,

methylone [ 2-methylamino-1- ( 3,4-

methylenedioxyphenyl)propan-1-one],

3.

TLC

Merck

HPTLC plates Silica gel 60F2542010 cm

0.2 mm

DOC [1-( 4-

(A)

Chloro-2,5-dimethoxyphenyl)propan-2-amine

10101(B)

252003

NMR

254 nm

HPLC TLC

10 1 ml 4

Fig. 1.

Structures of Chemical Drugs

a)Narcotic substances. b )Non controlled substances. No marked-compounds are designated substances.

hon p.3 [100%]

No. 6

983

25 ml 24 ml

5)

2C-I, 2C-C, DOI

2C-E, 2C-T-2, 2C-T-4

Tables 1 and 2

Fig. 1, Table 1 and 2

2,5 2C-B, DOB,

2C-T-7, DMA, DOM, DOET

DOC

1.

2,54

Table 1.
Type
Tryptamine

Piperazine

Phenethylamine

Colors produced by ve reagents with designated substances (Shitei-Yakubutsu)

Chemical
drugs

Marquis
reagent

Ehrlich
reagent

Simon's
reagent

Liebermann-Burehard's
reagent

5-MeO-MIPT
5-MeO-DMT

Dark brown
Dark brown

Grayish green
Grayish green

Dark brown
Dark brown

5-MeO-AMT

Dark brown

Grayish green

Brown

5-MeO-DALT
5-MeO-DPT

Brown
Brown

Grayish green
Grayish green

Dark brown
Dark brown

5-MeO-DET

Brown

Pale pink

Brown

4-OH-DIPT

Brown

Deep purple

Grayish blue

Dark brown

4-AcO-DIPT
DPT
DIPT
MIPT

Brown
Greenish brown
Pale brown
Greenish brown

Deep red purple

Red purple
Red purple
Red purple

Pale grayish blue

Dark brown
Brown
Brown
Brown

Greenish brown
Deep greenish
brown
Deep greenish
brown
Greenish brown
Deep greenish
brown
Deep greenish
brown
Deep greenish
brown
Greenish brown
Greenish brown
Greenish brown
Greenish brown

4MPP
MBZP
MDBP

Deep Red purple

Red purple
Yellowish red
Blue

Pale yellow
Yellow
Dark brown

Pale green
Yellowish brown
Deep brown

Deep green
Deep yellow green
Pale brown
Pale orange
Pale orange
Deep green

Deep blue

Brilliant orange
Deep purple blue
Deep purple blue
Greenish brown
Brilliant yellow
Brilliant yellow
Dark brown

Brilliant red

Pale red purple

Deep blue

2C-I
2C-C
2C-E
2C-T-2
2C-T-4
DOI
PMMA
4FMP
TMA-6
HMDMA
BDB
MMDA-2
bk-MBDB
bk-MDEA
2-aminoindan

Blue
Blue

Mandelin
reagent

Brown
Pale brown
Pale yellow green Pale yellow green
Yellow green
Yellow green
Purple
Purple
Purple
Purple
Pale brown
Yellow green
Deep red purple
Brown
Orange
Pale blue
Pale brown
Deep red
Deep brown
Deep brown
Dark brown
Dark brown
Yellow green
Brown
Greenish brown
Brown
Greenish brown
Brown
Yellowish brown
Dark blue

hon p.4 [100%]

984

Vol. 128 (2008)

Table 2. Colors produced by the Marquis reagents with

selected phenetylamines
Type

Phenethylamine

Chemical drugs
2C-C
2C-B a)
2C-I
2C-E
2C-T-2
2C-T-4
2C-T-7 a)
DOC b)
DOB a)
DOI
DMA a)
DOM a)
DOET a)
HMDMA
BDB
MMDA-2
bk-MBDB
bk-MDEA
Methylone a)

7)

Marquis reagent

2,4,6 TMA-6

Deep yellow green

Deep blue green
Deep green
Pale brown
Pale orange
Pale orange
Pale orange
Deep yellow green
Deep blue green
Deep green
Greenish brown
Pale yellow
Pale brown
Deep purple blue
Deep purple blue
Greenish brown
Brilliant yellow
Brilliant yellow
Brilliant yellow

3,4,5

a) Narcotic substances. b) Non controlled substances. No markedcompounds are designated substances.

TMA 2,4,5
TMA-2
data
not

shown

6) 5)
TMA-6

data not shown

TMA TMA-2 TMA-6

4MPP, MBZP, MDBP

PMMA, HMDMA, bk-MBDB, bk-MDEA

TMA-6 Table 1
4

2C-B, DOB, DOC

4-OH-DIPT 4-AcO-DIPT

Fig. 1, Table 24

Cl, Br, I 2,5

b bk-MBDB, bk-MDEA

b me-

Table

Fig. 1, Table 2
thylone

4MPP MBZP

HMDMA, BDB, MMDA-2

Table 2b

MDBP

cathinone, methcathinone data

not shownb

Fig. 2

TMA-6

Table 1

hon p.5 [100%]

No. 6

985

4MPP, MDBP A Rf
0.04 0.05
MBZP Rf 0.27
B Rf
0.360.330.48

2,5 2C-I,
2C-C, 2C-E, 2C-T-2, 2C-T-4, DOI
A 2C-I, 2C-C, 2C-T-2, 2C-T-4

2C-E DOI
Rf 0.42, 0.40 B
DOI Rf
0.43 Rf 0.31
0.34

A
N PMMA HMDMA Rf 0.11, 0.09 B

Rf 0.35, 0.28
4-FMP TMA-6, BDB,
Fig. 2. Proposed Flow Chart for Screening of Designated
Substances (Shitei-Yakubutsu) Using Color Test

MMDA-2, 2-aminoindan Rf A
B b

bk-MBDB bk-MDEA

A Rf 0.39, 0.43

B Rf 0.66, 0.69

2 TLC

Table 3

UV254 nm

HMDMA

5-MeO-DMT, 4MPP, PMMA, BDB

B 5MeO-AMT 4-

OH-DIPT

2.

TLC

A B Rf

Table 3

A, B

Rf

5-MeO-DMT, 5-MeO-AMT A

Rf 0.16, 0.14 B Rf

data not shown

0.43, 0.33 DIPT

A Rf 0.81

TLC

B Rf 0.56

TLC

hon p.6 [100%]

986

Vol. 128 (2008)

Table 3.

Type

Chemical drugs

TLC analyses of designated substances (Shitei-Yakugutsu)

Solvent A

Solvent B

(n-hexane/acetone/triethylamine10/10/1)

(MeOH/25 ammonia solution200/3)

Rf values a)

Color b)

Rf values a)

Color b)

Tryptamine

5-MeO-MIPT
5-MeO-DMT
5-MeO-AMT
5-MeO-DALT
5-MeO-DPT
5-MeO-DET
4-OH-DIPT
4-AcO-DIPT
DPT
DIPT
MIPT

0.41
0.16
0.14
0.70
0.73
0.43
0.67
0.61
0.77
0.81
0.37

Whitish yellow c)
Red
Red
Whitish red c)
Whitish yellow c)
Whitish yellow c)
Yellow
Yellow
Whitish yellow c)
Whitish yellow c)
Red

0.46
0.43
0.33
0.76
0.69
0.48
0.56
0.59
0.68
0.56
0.49

Red purple
Purple blue
White c)
Red purple
Red purple
Red purple
Yellow green
Pale purple
Red purple
Red purple
Red purple

Piperazine

4MPP
MBZP
MDBP

0.04
0.27
0.05

Red
Purple
Red

0.36
0.48
0.33

Red purple
Purple
Purple blue

Phenethylamine

2C-I
2C-C
2C-E
2C-T-2
2C-T-4
DOI
PMMA
4FMP
TMA-6
HMDMA
BDB
MMDA-2
bk-MBDB
bk-MDEA
2-aminoindan

0.34
0.33
0.42
0.32
0.36
0.40
0.11
0.36
0.27
0.09
0.51
0.32
0.39
0.43
0.45

Whitish orange c)
Whitish orange c)
Whitish orange c)
Orange
Orange
Whitish orange c)
Whitish yellow c)
Whitish orange c)
Orange
White c)
Red
Orange
Pale whitish yellow c)
Pale whitish yellow c)
Orange

0.32
0.32
0.32
0.31
0.34
0.43
0.35
0.47
0.30
0.28
0.58
0.39
0.66
0.69
0.45

Red purple
Purple
Red purple
Red purple
Red purple
Red purple
Pale red purple
Pale red purple
Pale blue
Purple
Pale purple
Pale blue
Red purple
Red purple
Purple blue

a) Detected by UV254 nm. b) Detected by an iodoplatinate reagent. c) Colored spot on gray background.

2C-I, 2C-T-2, 2C-T-4 3 20 1

18

REFERENCES
1)

Doi K., Miyazawa M., Fujii H., Kojima T.,

Yakugaku Zasshi, 126, 815823 (2006).

Takahashi M., Hirofumi M., Nagashima M.,
Seto T., Miyatake N., Suzuki J., Kamimura
H., Yasuda I., Ann. Rep. Tokyo Metr. Inst.
P.H., 54, 5155 (2003).
3) Kikura-Hanajiri R., Kawamura M., Uchiyama
N., Ogata J., Kamakura H., Saisho K., Goda
Y., Yakugaku Zasshi (in press).
4) U.S. National Institute of Justice, ``Color Test
Reagents/Kits for Preliminary Identication
of Drugs of Abuse,''http://www.ncjrs.gov/
pdles1/nij/183258.pdf. 2000.
, 10 Dec., 2007.
5 ) The Pharmaceutical Society of Japan,
``Yakudokubutsu Shikenho to Chukai 2006

2)

hon p.7 [100%]

No. 6

6)

987

Bunseki Dokusei Taishoho,'' Tokyo Kagaku

Dojin, Tokyo, 2006.
The Pharmaceutical Society of Japan,
``Yakudokubutsu Kagaku Shikenho to Chukai,'' 4th ed., Nanzando, Tokyo, 1992.

7)

Moat A. C., Osselton M. D., Widdop B.,

``Clarke's Analysis of Drugs and Poisons,''
3rd ed., Vol. 1, Pharmaceutical Press, London, 2004.