KHAT Latest Revision: June 11, 2005

O
CH3

NH2

Cathinone

OH
CH3

NH2

Cathine

N CH3

H3C N

3,6-dimethyl-2,5-diphenylpyrazine
(dimer of Cathinone)

1. SYNONYMS

CFR: Cathinone
Cathine

CAS #: Cathinone Hydrochloride: 71031-15-7

Cathine Hydrochloride: 2153-98-2
Cathine Base: 492-39-7

Other Names: Catha edulis

Kat
Mutsawhari
Mutsawari
Mdimamadzi
Musitate
Mirungi
Miraa
Ol meraa
 Tumayot
Liruti
Ikwa
Arabian Tea

2. CHEMICAL AND PHYSICAL DATA

Khat is used as a stimulant or as a medicine in parts of Africa and the Arabian Peninsula. The plant is thought
to have been in cultivation before the coffee plant; historical references date the use of the plant to the
fourteenth century. Peter Forsskal, a physician and botanist, collected khat specimens in an expedition
organized by the King of Denmark in the eighteenth century. Forsskal assigned the name Catha edulis to the
plant.

The effects produced by the drug include excitation, hypersensitivity, anorexia, insomnia, euphoria, increased
respiration, and hyperthermia. These effects closely parallel the effects of d-amphetamine.

Khat is a bush or tree that grows naturally in the humid mountainous regions (elevations of 5000 to 6500 feet)
of East and South Africa. The trees can grow naturally to over 60 ft; however, cultivated khat trees are pruned
and their height to kept to approximately 16 feet. Khat also grows to a height of 3 feet as a small bush in arid
regions. Like opium, the alkaloid content of khat will vary with the soil, climatic conditions, and cultivation.
Khat belongs to the genus Catha edulis. It is recognized that the genus consists of only one species; however,
the plant exhibits extreme polymorphism. The plant comprises several cultural varieties, which do not have the
same properties. The leaves may be thin and narrow or very broad. The leaves may be arranged on a branch in
opposite pairs, but are sometimes displaced resulting in an alternating orientation. New leaves are a reddish-
brown color, becoming greenish-yellow when fully grown. The leaves are bifarious (arranged in two rows),
elliptical, lanceolate with sharp edges and coriaceous (leather like). Some have reported the leaves to be almost
tasteless, while others report the leaves are aromatic, sweet, and astringent. Dimensions of the leaves vary from
0.5 cm to 7 cm in length.

The khat plant will produce small, white, or light green flowers. The flowers will be arranged in auxiliary
cymes (a flower cluster, in which the main axis and branch end in a flower will open before the flowers below
or to the side of it). The flowers have five equal sepals and five oblong petals.

Khat can be used in a variety of ways. Fresh plant material is generally chewed for the stimulant effect of the
cathinone. Large leaves or dried leaves are powdered in a mortar. The powdered material is then mixed with
sugar and sometimes spices and water making a paste, which is chewed. Dried leaves can also be brewed into a
tea, or alternatively, the leaves can be crushed and rolled into cigarettes.

Khat is quality rated by connoisseurs in a manner similar to tea and coffee. The criteria utilized depend upon
the part of the plant that will be used – leaves, buds, or twigs. This is coupled with the degree of maturity, the
size of the leaf and the area of plant origin. Larger and older leaves will be tough and not easily chewed.
Additionally, these leaves will contain a lower amount of cathinone as compared to younger leaves from the
same plant. In addition, the red leaf type known as “dimma” is known to have more cathinone than the white
leaf type known as “dallota”.

Three to six alkaloids have been identified in khat. The principle active alkaloid in khat is S-(-)- -
aminopropriophenone, or (-)-cathinone. In some khat samples this compound accounts for up to 70% of the
phenylalkylamine fraction. The content of the (-)-cathinone is directly associated with the market price of khat.
Cathinone exists in khat as the racemic mixture; the total cathinone content can vary with reported values
ranging from 0.9% up to 3.3% in a Kenyan khat sample. Other phenylalkylamines present in khat include (+)-
norpseudoephedrine (cathine), norephedrine and 1-phenyl-1,2-propanedione.

The (-)-cathinone in the leaf material will begin to degrade to cathine and (-)-norephedrine once the leaf has
been harvested. Traditionally, the conversion process is slowed by tightly wrapping the leaves in moist false
banana leaves to retain moisture. The freshly harvested leaves can be air dried or frozen to preserve the (-)-
cathinone. Air-dried leaf material had detectable levels of (-)-cathinone after ten days and frozen leaf material
had detectable levels of (-)-cathinone after one year. Cathinone base will also dimerize in the presence of
oxygen to form 3,6-dimethyl-2,5-diphenylpyrazine.

large and small Khat leaves

red Khat leaf
 Left: top side of Khat leaf
Right: bottom side of Khat leaf
2.1. CHEMICAL DATA
Form Chemical Formula Molecular Weight Melting Point (°C)
Cathinone base C9H11NO 149.2 amu 77-78
Cathine Hydrochloride C9H13NO HCl 187.7 amu 180-181
3,6-dimethyl-2,5- C18H16N2 260.3 amu
diphenylpyrazine

2.2. SOLUBILITY

Cathinone and cathine are soluble in ethyl ether, hexane, chloroform and alcohol.

3. SCREENING TECHNIQUES

3.1. MICROSCOPIC EXAM

A microscopic examination of the leafy material should be conducted to note the general leaf characteristics.

3.2. COLOR TESTS

Color tests performed directly on plant material will not yield results. Extracted and purified material may give
the following results.

REAGENT COLOR PRODUCED

Cathine
Marquis No color development
Sodium Nitroprusside Rose
Cathinone
Marquis No color development
Sodium Nitroprusside Rose

3.3. THIN LAYER CHROMATOGRAPHY

Visualization

UV light Ninhydrin reagent

COMPOUND RELATIVE Rf and COLOR

UV light Ninhydrin spray
Cathine 0.26, brown 0.26, purple
Cathinone 0.48, brown 0.48, orange
Ephedrine 0.17, brown 0.17, purple
Phenylpropanolamine 0.26, red 0.26, orange
 Pseudoephedrine 0.23, brown 0.23, no color
Developing Solvent: ethyl acetate – methanol – ammonia (85 : 10 : 5)

3.4. GAS CHROMATOGRAPHY

Method General Screen1

Instrument: Gas chromatograph operated in split mode with FID

Column: 5% diphenyl/95% dimethylsiloxane 15 m x 0.25 mm x

0.25 µm film thickness

Carrier gas: Helium at 1.6 mL/min

Temperatures: Injector: 275°C

Detector: 280°C
Oven program:
1) 100°C initial temperature for 2.0 min
2) Ramp to 300°C at 15 degrees/min

Injection Parameters: Split Ration = 35:1, 1 µL injected

Samples extracted with 1N NaOH into chloroform and filtered.

COMPOUND RRT
amphetamine 0.694
methamphetamine 0.865
cathinone 1.000
cathine 1.003
1S,2R-(d)- 1.340
phenylpropanolamine
1S,2R-(d)-ephedrine 1.456
1S,2S-(d)- 1.470
pseudoephedrine
4. SEPARATION TECHNIQUES

The khat alkaloids are separated from the plant material by acid / base extractions into solvents. The khat
alkaloids can then be separated by GC, HPLC or TLC and identified with GC-IRD or GC-MSD.

Extraction scheme A
Five grams of leafy material is macerated in a plant mill or torn into very small pieces. Ten milligrams of
oxalic acid and 50 mL of water are added to the leafy material and either mechanically blended for three, one-
minute increments or sonicated for 15 minutes. The mixture is filtered through a Buchner funnel to separate the
liquid from the solid plant material. The liquid material is made basic (pH 9) with saturated sodium bicarbonate
and extracted into two 10 mL aliquots of chloroform. The chloroform aliquots are combined and evaporated to
near dryness under a stream of air. This extract can then be analyzed by GC, HPLC, TLC, GC-IRD or GC-MS.

Extraction scheme B
Five grams of leafy material is macerated in a plant mill or torn into very small pieces. Fifteen to 20 mL of
methanol is added and sonicated for 15 minutes. The mixture is filtered through a Buchner funnel to separate
the liquid from the solid plant material. The alcohol solution is evaporated to near dryness under a stream of
air. The small volume is reconstituted in 0.02 N sulfuric acid, extracted into chloroform, and separated. The
aqueous acidic layer is made basic with saturated sodium bicarbonate and extracted into dichloromethane. This
extract can then be analyzed by GC, HPLC, TLC, GC-IRD or GC-MS.

5. Quantitative Procedures

N/A

6. Qualitative Data

6.1. Ultraviolet Spectroscopy

COMPOUND SOLVENT MAXIMUM

ABSORBANCE (NM)
cathine 0.1 N H2SO4 249
cathinone 0.1 N H2SO4 256, 250, 262

See spectra on the following pages for FT-IR, Mass Spectrometry, FT-Raman, Nuclear Magnetic Resonance,
and Vapor Phase IR..

7. REFERENCES

Brenneisen, R. and Geisshusler, S., “Psychotropic Drugs”, Pharmaceutica Acta Helvetiae, Vol. 60, No. 11,
1985, pp. 290-301.

Bulletin on Narcotics, “Khat”, Vol. 8, No. 4, Oct. – Dec. 1956, pp. 6-13.

Clarke, E.G.C., Isolation and Identification of Drugs, 2nd Edition, The Pharmaceutical Press, 1986.

Geisshusler, S. and Brenneisen, R., “The Content of Psychoactive Phenylpropyl and Phenylpentyl Khataminesw
in Catha Edulis Forsk. Of Different Origin”, Journal of Ethnopharmacology, Vol 19, 1987, pp. 269-277.
Kalix, P., “Pharmacological Properties of the Stimulant Khat”, Pharmac. Ther, Vol 48, pp. 397-416, 1990.

Kalix, Peter and Khan, Inayat, “Khat: an amphetamine-like plant material”, Bulletin of the World Health
Organization, 62, (5), pp. 681-686, 1984.

Lee, M. M., “The Identification of Cathinone in Khat (Catha edulis): A Time Study”, Journal of Forensic
Sciences, Vol. 40, No. 1, January 1995, pp. 116-121.

Szendrei, K., “The Chemistry of Khat”, Bulletin on Narcotics, Vol. 32, No. 3, 1980, pp. 5-35.

Mathys, K. and Brenneisen, R., “HPLC and TLC Profiles of Phenylalkylamines of Khat (Catha edulis Forsk.)
Confiscated in Switzerland”, Pharmaceutica Acts Helvetiae, Vol. 68, 1993, pp. 121-128.

Morselli, O., Bovolenta, A., Ripani, L.,and Garofano, L., “Gas – Chromatography / Mass Spectrometry
Determination of the Active Principles of “Catha Edulis” African Vegetable”, Microgram, Vol. 35, No. 11,
Nov., 1992, pp. 290-294.

Nordal, A., and Laane, M. M., “Identification of Khat”, Medd. Norsk Farm. Selsk., Vol. 40, 1978, pp. 1-18.

United Nations Narcotics Laboratory, “Studies on the Chemical Composition of Khat. III. Investigations on
the phenylalkylamine fraction”, MNAR/11/1975.

United Nations Narcotics Laboratory, “Studies on the Chemical Composition of Khat. IX. The
phenylalkylamines of Catha edulis Forsk. The absolute configuration of cathinone”, MNIR/7/1978.

8. ADDITIONAL RESOURCES

Forendex (cathinone, cathine)

Wikipedia
 UV: Cathinone standard in 0.1 N H2SO4
1.20

1.1

1.0
249.30

0.9

0.8

0.7

0.6
A
0.5

0.4

0.3

0.2

0.1

-0.02
220.0 240 260 280 300 320 340 360 380 400.0
nm

UV: Cathine standard in 0.1 N H2SO4

1.71

1.6

1.4

1.2
256.76

250.94
1.0 262.80

A 0.8

0.6

0.4

0.2

-0.02
220.0 240 260 280 300 320 340 360 380 400.0
nm
 MS: Cathine
A
bun
dan
ce

S
can5
98(4
.64
6min
):c
ath
ine
.D
3
400
000 4
4

3
200
000

3
000
000

2
800
000

2
600
000

2
400
000

2
200
000

2
000
000

1
800
000

1
600
000

1
400
000

1
200
000

1
000
000

8
000
00

6
000
00
7
7

4
000
00

2
000
00 5
1
1
05
6
3 9
1 1
17
5
7 7
2 8
6 9
8 1
27 1
32 1
52
0
4
0 5
0 6
0 7
0 8
0 9
0 1
00 1
10 1
20 1
30 1
40 1
50
m
/z
-->

MS: Cathinone
A
bun
dan
ce

S
can5
78(4
.54
0min
):c
ath
ino
ne.D
3
200
000 4
4

3
000
000

2
800
000

2
600
000

2
400
000

2
200
000

2
000
000

1
800
000

1
600
000

1
400
000

1
200
000

1
000
000

8
000
00
7
7
6
000
00
5
1
4
000
00
1
05
2
000
00

5
7 6
3 7
0 8
9 9
8 1
16 1
28 1
34 1
50
0
4
0 5
0 6
0 7
0 8
0 9
0 1
00 1
10 1
20 1
30 1
40 1
50
m
/z
-->
 MS: 3,6-dimethyl-2,5-diphenylpyrazine
Cathinone dimer
Abundanc
e

32000 115

30000 259
28000
26000
24000
22000
20000
18000
16000
14000
12000
10000
8000
6000
4000 89 103
44 63 77
2000
130 148 207 218 235 281
173
0
40 60 80 100 120 140 160 180 200 220 240 260 280
m/z-->

RAMAN:: Cathine HCl standard

16 scans, 8 cm-1 resolution

40

35

30
Raman intensity

25

20

15

10

3000 2000
2000 1500 1000 500
Raman shi ft (cm-1)
 RAMAN: Cathinone HCl
6 scans, 8 cm-1 resolution
28

26

24

22

20

18
R aman intensity

16

14

12

10

3000 2000 1500 1000 500

Raman shift (cm-1)

FTIR: Cathine HCl standard, KBr pellet.

16 scans, 2 cm-1 resolution
55

50

45

40

35
% Trans mittanc e

30

25

20

15

10

3000 2000 1500 1000 800 600

W avenumbers (cm-1)
 FTIR: Cathinone HCl standard, KBr pellet.
16scans, 2 cm-1 resolution
70

65

60

55

50

45
% Trans mittanc e

40

35

30

25

20

15

10

3000 2000 1500 1000 800 600

W avenumbers (cm-1)

IR (Vapor Phase): Cathine

Optical resolution 1.58 cm/s
100.5

100

99.5

99

98.5

98

4000 3000 2000 1000

Wavenumber (cm-1)
 IR (Vapor Phase): Cathinone
Optical resolution 1.58 cm/s

100

99

98

97

96

4000 3000 2000 1000

Wavenumber (cm-1)

NMR (Proton): Cathinone

CD3Cl, 8 repetitions
4.85

1.0

0.9

0.8

0.7
Normalized Intensity

0.6

0.5
4.84

0.4
3.30

0.3
3.31

1.57
1.55

0.2
4.86
8.03

7.59
8.06

1.54
7.61
8.04

7.72

7.57

0.1

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)
 NMR (Proton): Cathine hydrochloride
CD3Cl, 8 repetitions

4.84
1.0

0.9

0.8
7.38
0.7
Normalized Intensity

1.08
0.6

0.5

0.4

3.28
0.3

4.47
0.2

0.1

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical Shift (ppm)