Synthetic cathinones are related to the parent compound cathinone (Figure 1), one of the

psychoactive principals in khat (Catha edulis Forsk). Cathinone derivatives are the -keto (k)
analogues of a corresponding phenethylamine. The group includes several substances that have
been used as active pharmaceutical ingredients (API) of medicinal products, e.g. amfepramone
(diethylpropion; Figure 2). Since the mid-2000s, unregulated ring-substituted cathinone
derivatives have appeared in the European recreational drugs market. The most commonly
available cathinones sold on the recreational market in the period up to 2010 appear to be
mephedrone (Figure 3) and methylone (Figure 4). These products are usually encountered as
highly pure white or brown powders. Ring-substituted cathinone derivatives are claimed to have
effects similar to those of cocaine, amphetamine or MDMA (ecstasy), but little is known of their
detailed pharmacology. Apart from cathinone (Figure 1), methcathinone (Figure 5) and two
APIs amfepramone (Figure 2) and pyrovalerone, cathinone derivatives are not under
international control.

Chemistry
Figures 17 show the naturally occurring cathinone (Figure 1) and six synthetic derivatives
(Figures 27).

Figure 1: Cathinone

Molecular formula: C9H11NO

Molecular weight: 149.19 g/mol

Figure 2: Amfepramone (diethylpropion)

Molecular formula: C13H19NO

Molecular weight: 205.30 g/mol

Figure 3: Mephedrone (4-methylmethcathinone, 4-MMC)

Molecular formula: C11H15NO

Molecular weight: 177.24 g/mol

Figure 4: Methylone (k-MDMA, 3,4-methylenedioxy-N-methylcathinone)

Molecular formula: C11H13NO3

Molecular weight: 207.22 g/mol

Figure 5: Methcathinone (ephedrone)

Molecular formula: C10H13NO

Molecular weight: 163.22 g/mol

Figure 6: MDPV (3,4-methylenedioxypyrovalerone)

Molecular formula: C16H21NO3

Molecular weight: 275.35 g/mol

Figure 7: Methedrone (k-PMMA, 4-methoxymethcathinone)

Molecular formula: C11H15NO2

Molecular weight: 193.24 g/mol
Cathinone (Figure 1) and its derivatives are closely related to the phenethylamine family. Thus
cathinone itself is -keto (k) amphetamine, 2-aminopropiophenone or, more formally, 2-amino1-phenyl-1-propanone (IUPAC systematic name). The first synthetic cathinone that appeared in
the recreational drug market, methcathinone (Figure 5), is k-methamphetamine, ephedrone or
N-methylcathinone. Most of the unregulated cathinone derivatives that have been marketed in
the past few years are ring-substituted, the most prevalent of which appears to be mephedrone (4methylmethcathinone, 4-MMC, Figure 3). Some products sold are also likely to contain a
mixture of different chemicals. Other cathinones reported to the Early warning system on new
drugs include methylone (k-MDMA; 3,4-methylenedioxy-N-methylcathinone, Figure 4),
MDPV (3,4-methylenedioxypyrovalerone, Figure 6), methedrone (k-PMMA; 4methoxymethcathinone, Figure 7) and PPP (-pyrrolidinopropiophenone).
Like the phenethylamines, cathinone derivatives can exist in two stereoisomeric forms, which
may differ in their potencies. The cathinone that occurs naturally in khat is the S-enantiomers.
However, it is likely that most ring-substituted derivatives are racemic mixtures. It is also
believed that racemisation of all cathinone derivatives can occur through keto-enol tautomerism.
Cathinone is labile and transforms to a dimer (3,6-dimethyl-2,5-diphenylpyrazine). Cathinone
derivatives can also rearrange via a dihydropyrazine dimer to form so-called isocathinones; All
known cathinone derivatives are either N-alkylated or the nitrogen atom is part of a pyrrolidine
ring, and most are produced as hydrochloride salts. Many illicit products are N-methylated, i.e.
ephedrone derivatives, whereby mephedrone can be described as 4-methylephedrone. The
pyrrolidine derivatives (PPP, MDPV) can be regarded as a sub-set of designer drugs sharing the
same skeleton as pyrovalerone. Table 1 lists those cathinone derivatives that have been used as
API, found in drug seizures, samples collected for monitoring purposes or offered for sale on
Internet sites (see Figure 8). Naphyrone (1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one), a
more complex cathinone derivative, is not included in Table 1.

Figure 8: General structure of a cathinone derivative showing substitution

patterns

Table 1
The structural classification of cathinone derivatives found in drug seizures, collected samples or
offered for sale on Internet sites (see Figure 8). Those that are or have been used as active
pharmaceutical ingredients (API) are shown emboldened.
R1
R2
R3
H
H
H
Methyl H
H
Methyl Methyl H
Ethyl H
H
Methyl H
H
Ethyl H
4-Methyl
Methyl H
4-Methyl
Ethyl Ethyl H
t-Butyl H
3-CI
3,4Methyl H
Methylenedioxy
3,4Ethyl H
Methylenedioxy
Methyl H
4-Methyl
Methyl H
4-Methoxy
Methyl H
4-F
Methyl H
3-F

R4
R5
H
H
H
H
H
H
H
H
Methyl H
H
H
H
H
H
H
H
H

Name
Cathinone
Methcathinone (ephedrone)
N,N-Dimethylcathinone (metamfepramone)
N-Ethylcathinone (EC)
Buphedrone
4-Methyl-N-ethylcathinone
Mephedrone (4-MMC; M-CAT)
Amfepramone
Bupropion

Methylone (k-MDMA)

Ethylone (k-MDEA)

Methyl H
H
H
H
H
H
H

Butylone (k-MBDB)
Methedrone (k-PMMA)
Flephedrone (4-FMC)
3-Fluoromethcathinone (3-FMC)

{pyrrolidino} H

-Pyrrolidinopropiophenone (PPP)

{pyrrolidino} 4-Methyl

4-Methyl--pyrrolidinopropiophenone
(MPPP)

R1

R2

{pyrrolidino}

R3
4-MeO

{pyrrolidino} 4-Methyl
{pyrrolidino} 4-Methyl
{pyrrolidino} 4-Methyl
{pyrrolidino} 4-Methyl
3,4Methylenedioxy
3,4{pyrrolidino}
Methylenedioxy
{pyrrolidino}

R4

R5

Name
4-methoxy--pyrrolidinopropiophenone
H
H
(MOPPP)
4-Methyl--pyrrolidino-hexanophenone
Propyl H
(MPHP)
Ethyl H
Pyrovalerone
4-Methyl--pyrrolidino-butyrophenone
Methyl H
(MPBP)
4-Methyl--pyrrolidino-H
Methyl
methylpropiophenone
3,4-Methylenedioxy-H
H
pyrrolidinopropiophenone (MDPPP)
Ethyl H

3,4-Methylenedioxypyrovalerone (MDPV)

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Physical form
Synthetic cathinones are mostly encountered as white or brown amorphous or crystalline
powders, occasionally encapsulated. Unlike many phenethylamine derivatives (MDMA, etc.),
tablets are less common but are sometimes available on the illicit market, presumably as a
replacement for MDMA.
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Pharmacology
As with phenethylamines, in the absence of ring-substitution, cathinones behave as central
nervous system (CNS) stimulants, although invariably with a lower potency than the
corresponding phenethylamine analogue. The lower potency is caused by the -keto group
creating a more polar molecule less able to cross the bloodbrain barrier. Studies on the
metabolism of methcathinone derivatives in rats and humans have shown that they are Ndemethylated, the keto group is reduced to hydroxyl, and ring alkyl groups are oxidised.
Otherwise, few formal studies have been made on the pharmacokinetics or pharmacodynamics of
ring-substituted cathinones. From observations of patients who presented with suspected
mephedrone toxicity, it appears that cathinone derivatives show similar sympathomimetic effects
to amphetamine derivatives. The first toxicologically confirmed fatal case directly linked to
mephedrone use was recorded in Sweden in 2008.
User reports on Internet sites suggest that a typical dose of mephedrone is 100250 mg.
Depending on the particular substance, the effects are claimed to be similar to those of cocaine,
amphetamine or MDMA. Like cocaine, the resulting high of mephedrone is short-lived.
Consequently, users may consume several doses in succession, up to 1 g in a session. This is

supported by the finding that the most common wrap size of mephedrone found in police
seizures in the United Kingdom is close to 750 mg.
The pyrrolidine ring and the tertiary amino group in MDPV could lead to a more lipophilic, i.e.
more potent, molecule; Internet user-forums suggest that the dose is as low as 510 mg.
Furthermore, it should be noted that p-methoxyphenethylamines (e.g. PMA, PMMA) are known
to have a particularly high toxicity, and this property might translate to their k-analogues. For
example, methedrone (p-methoxymethcathinone) has been detected in a few fatalities.
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Synthesis and precursors

Simple derivatives such as methcathinone and N,N-dimethylcathinone can be synthesised by
oxidation of ephedrine (or pseudoephedrine) and N-methylephedrine (or Nmethylpseudoephedrine) respectively. This requires reacting the precursor with a solution of
potassium permanganate in dilute sulfuric acid. The precursors can be obtained as specific
enantiomers, thereby ensuring that the synthesis is stereoselective. Cathinone itself can be made
in a similar way, starting from phenylpropanolamine (norephedrine). One of the hazards of the
permanganate process is that users can suffer manganese poisoning if the product is not purified.
The ring-substituted N-methylcathinone derivatives are best synthesised by reacting the suitably
substituted bromopropiophenone with methylamine; the result is always racemic. In the case of
methylone, for example, 2-bromo-3,4-methylenedioxy-propiophenone can be prepared by
reacting 3,4-methylenedioxypropiophenone with bromine. These precursor substances are
readily available and none of them is under international control. Other methods are required to
produce the pyrrolidine derivatives, but apart from MDPV, substances such as PPP, MPHP,
MOPPP and MDPPP, which briefly appeared in Germany in 2004 (see Table 1), have since been
rarely observed.
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Mode of use
Some users insufflate (snort) mephedrone, but most of the cathinones are ingested. Since they are
soluble in water, these substances can also be injected. Because of their lability, the free bases
would probably not be suitable for smoking.
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Other names
To circumnavigate possible controls, suppliers of cathinone derivatives often market them under
various brand names (e.g. Explosion, Blow, Recharge, etc.) as plant food, bath salts, or
research chemicals, often with a printed warning that they are not for human consumption. As

with the phenethylamines, acronyms are common. Thus MDPV stands for 3,4methylenedioxypyrovalerone, 4-FMC for 4-fluoromethcathinone (flephedrone), and 4-MMC for
4-methylmethcathinone (mephedrone). User names for mephedrone include M-Cat, meph, drone,
miaow, meow meow, subcoca-1 and bubbles; while methylone is sometimes known as Top Cat.
However, these substances are often sold in products that have a large number of brand names
that change rapidly over time and where the specific content is often not given. The chemical
names can lead to confusion; methylone, mephedrone and methedrone should be distinguished
from each other and from the unrelated narcotic analgesic methadone. Although k-MBDB is
often described as butylone, butylone has also been used as a proprietary name for the
unrelated barbiturate pentobarbital.
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Analysis
Cathinone derivatives do not give a coloured reaction with the Marquis field test. Analysis using
GCMS and Infrared (IR) spectroscopy is straightforward. Although pure reference samples of
some derivatives may not be commercially available, analytical profiles for most have been
published. Immunoassay field tests for methamphetamine give false positive reactions with some
cathinone derivatives.
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Typical purities
Some powders containing mephedrone and related compounds have been adulterated with other
drugs such as ketamine, cocaine, paracetamol or piperazine derivatives, but most appear to be
highly pure as judged by IR spectroscopy.
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Control status
Cathinone and methcathinone are listed in Schedule I of the United Nations 1971 Convention on
Psychotropic Substances. Amfepramone and pyrovalerone are in Schedule IV of that
Convention, but other derivatives are not under international control. A few cathinone derivatives
are controlled in some Member States under drug control or equivalent legislation, for example:
mephedrone (Belgium, Denmark, Germany, Estonia, Ireland, France, Italy, Lithuania, Romania,
Sweden, Croatia and Norway); methylone (Denmark, Ireland, Romania and Sweden); butylone
(Denmark, Ireland, Romania, Sweden and Norway); MDPV (Denmark, Ireland, Finland and
Sweden); and flephedrone (Denmark, Ireland and Romania). Generic control in the United
Kingdom covers a wide group of cathinone derivatives. Mephedrone is controlled under
medicines legislation in Finland and the Netherlands and Finland.

By Council Decision of 2 December 2010, 4-methylmethcathinone (mephedrone) was submitted

to control measures in EU Member States (2010/759/EU).
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Prevalence
Synthetic cathinones have only recently appeared on the recreational drugs market, and few
formal epidemiological studies have been published. There are no nationwide studies within the
EU on the prevalence of mephedrone use in any given population. In an online survey conducted
in late 2010 in collaboration with the United Kingdoms dance music magazine Mixmag,
mephedrone was the fourth most-commonly used drug in the past year (after cannabis, ecstasy
and cocaine) and had been tried by 61 % of respondents. 25 % of respondents had tried it within
the last month, which was a decrease compared to 33.6% in late 2009. It should be noted that
mephedrone was scheduled in the UK mid-april 2010.
Although not controlled in many countries, synthetic cathinones are regularly submitted to
forensic laboratories by police and customs for identification. The number of such submissions
increased rapidly during the second half of 2009. Methylone was one of the first ring-substituted
synthetic cathinones to be reported in the EU (Netherlands, Sweden, 2005), but mephedrone has
become the most commonly seen derivative. Information on seizures and samples from the
Netherlands indicate that tablets sold as ecstasy, but actually containing mephedrone (sometimes
in combination with MDMA), appeared on the market for the first time in 2009. However, the
absence of systematic data makes it difficult to comment with confidence on the availability of
different cathinone products, although reports do suggest that availability varies over time and
place.
Up until the introduction of control measures in the UK in April 2010, mephedrone and other
synthetic cathinones were readily available either from Internet suppliers or retail outlets. An
EMCDDA snapshot of the availability of mephedrone on the Internet in March 2010 showed that
at least 77 websites, would sell and ship the substance to a user in the EU. In July 2011, 18
websites were identified claiming to sell mephedrone.
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Street price
Mephedrone and related compounds are primarily sold on websites or in head shops. The 2010
EMCDDA snapshot showed prices ranging between EUR 10 and 15 for one gram, with
discounts offered for bigger quantities. In the 2011 EMCDDA snapshot prices were ranging
between EUR 18 and 25 for one gram.
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Medical use

Amfepramone and pyrovalerone have been used as anorectics, but are now largely obsolete.
Bupropion has antidepressant properties and is used as an aid for those who wish to quit tobacco
smoking.
katinona sintetis terkait dengan senyawa induk cathinone (Gambar 1), salah satu
pelaku psikoaktif di khat (Catha edulis Forsk). derivatif cathinone adalah -keto (k)
analog dari phenethylamine yang sesuai. Kelompok ini mencakup beberapa zat
yang telah digunakan sebagai bahan aktif farmasi (API) dari produk obat, misalnya
amfepramone (diethylpropion; Gambar 2). Sejak pertengahan 2000-an, tidak diatur
cincin tersubstitusi turunan cathinone telah muncul di pasar narkoba Eropa. The
katinona yang paling umum tersedia dijual di pasar rekreasi pada periode hingga
2010 tampak mephedrone (Gambar 3) dan metilon (Gambar 4). Produk-produk ini
biasanya ditemui sebagai bubuk putih atau coklat yang sangat murni. derivatif
cathinone cincin tersubstitusi yang diklaim memiliki efek mirip dengan kokain,
amfetamin atau MDMA (ekstasi), tetapi sedikit yang diketahui farmakologi rinci.
Terlepas dari cathinone (Gambar 1), methcathinone (Gambar 5) dan dua API
amfepramone (Gambar 2) dan pyrovalerone, turunan cathinone tidak berada di
bawah pengawasan internasional.
Cathinone (Gambar 1) dan turunannya terkait erat dengan keluarga
phenethylamine. Jadi cathinone itu sendiri adalah -keto (k) amfetamin, 2aminopropiophenone atau, lebih formal, 2-amino-1-fenil-1-propanon (IUPAC nama
sistematis). The cathinone sintetis pertama yang muncul di pasar narkoba,
methcathinone (Gambar 5), adalah k-methamphetamine, ephedrone atau Nmethylcathinone. Sebagian besar turunan cathinone tidak diatur yang telah
dipasarkan di beberapa tahun terakhir adalah cincin tersubstitusi, yang paling
umum yang tampaknya menjadi mephedrone (4-methylmethcathinone, 4-MMC,
Gambar 3). Beberapa produk yang dijual juga mungkin mengandung campuran
bahan kimia yang berbeda. katinona lainnya dilaporkan ke sistem peringatan dini
pada obat baru termasuk metilon (k-MDMA; 3,4-methylenedioxy-Nmethylcathinone, Gambar 4), MDPV (3,4-methylenedioxypyrovalerone, Gambar 6),
methedrone (k-PMMA; 4-methoxymethcathinone, Gambar 7) dan PPP (pyrrolidinopropiophenone).
Seperti phenethylamines, turunan cathinone bisa eksis dalam dua bentuk
stereoisomer, yang mungkin berbeda dalam potensi mereka. The cathinone yang
terjadi secara alami dalam khat adalah S-enantiomer. Namun, ada kemungkinan
bahwa sebagian besar turunan cincin diganti adalah campuran rasemat. Hal ini juga
percaya bahwa rasemisasi dari semua turunan cathinone dapat terjadi melalui ketoenol tautomerisme. Cathinone labil dan mengubah ke dimer (3,6-dimetil-2,5diphenylpyrazine). derivatif cathinone juga dapat mengatur ulang melalui dimer
dihydropyrazine untuk membentuk apa yang disebut 'isocathinones'; Semua
turunan cathinone dikenal yang baik N-alkilasi atau atom nitrogen merupakan
bagian dari cincin pirolidin, dan sebagian besar diproduksi sebagai garam
hidroklorida. Banyak produk terlarang yang N-metilasi, yaitu turunan ephedrone,

dimana mephedrone dapat digambarkan sebagai 4-methylephedrone. The

pyrrolidine derivatif (PPP, MDPV) dapat dianggap sebagai sub-set 'obat desainer'
berbagi kerangka yang sama seperti pyrovalerone. Tabel 1 daftar turunan cathinone
yang telah digunakan sebagai API, ditemukan dalam kejang obat, sampel yang
dikumpulkan untuk tujuan monitoring atau ditawarkan untuk dijual di situs Internet
(lihat Gambar 8). Naphyrone (1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-satu),
sebuah cathinone derivatif yang lebih kompleks, tidak termasuk dalam Tabel 1.

Liquid Chromatograpy Mass Spectroscopy adalah dua alat yang digabungkan menjadi
satu, yang berfungsi untuk memisahkan beberapa senyawa atau campuran senyawa berdasarkan
kepolarannya (prinsip kerja kromatografi), dimana setelah campuran senyawa tersebut terpisah,
maka senyawa yang murni akan diidentifikasi berat molekulnya. Data yang didapatkan adalah
berat molekul ditambah beberapa muatan dan berat molekul pelarut.
Adapun cara kerja liquid chromatograpy adalah sama dengan HPLC atau liquid
a.

chromatograpy lain, adalah :

Analit bersama dengan eluen dari syringe pump atau LC masuk ke dalam cappilary. Di dalam
cappilary terdapat anoda (kutup negatif) pada taylor cone dan katoda (kutup negatif) di dekat
masukan analit dan eluen. Kutup ini berfungsi agar muatan yang berkumpul pada taylor cone
adalah muatan positif sehingga nantinya saat terjadi penyemprotan dan terbentuk droplet (tetes

tetes) tidak bergabung gabung menjadi droplet yang lebih besar lagi.
b. Analit dan solven(eluen) disemprotkan melalui taylor cone.
Akan terbentuk droplet droplet dimana droplet droplet itu akan mengalami tahap evaporasi
solven untuk mengurangi solven yang menempel di analit. Karena suatu saat, apabila terjadi
evaporasi secara terus menerus maka solven yang meliputi analit terkungkung dalam muatan
positif yang berlebih, dalam bahasa Inggris tahap seperti ini disebut the rayleigh limit is
reached, maka akan terjadi explosion yang disebut coulombic explosion dimana akan terjadi
pemecahan droplet (tetesan) tadi. Ada beberapa kemungkinan yang terjadi pada droplet droplet
tersebut, yaitu :

1)
2)
3)
4)
5)
c.

analit akan tertambahi satu muatan positif

analit akan tertambahi beberapa muatan positif
analit akan tertambahi satu muatan positif dan satu molekul solven
analit akan tertambahi satu muatan positif dan beberapa molekul solven
analit akant tertambahi beberapa muatan positif dan beberapa molekul solven.
Droplet yang mengalami coulombic exsploison tersebut akan masuk ke dalam cone dimana di
sisi kiri dan kanannya sudah mengalir gas Nitrogen (N2). Gas ini berfungsi agar analit yang
terjadi tadi stabil dalam bentuknya dan tidak terganggu oleh pengaruh gas oksigen. Droplet
masuk ke dalam cappilary transfer lalu akan dianalisis melalui mass spectrometer.
Muatan positif pada solven berasal dari ion-ion Na +, Li+, K+, NH4+, dan kation lain. Oleh
karena pada daerah taylorcone dalam capillary nedle bermuatan negatif,maka analit dalam
solven yang memiliki muatan positif akan berkumpul didaerah taylorcone. Akibatnya pada saat
penyemprotan tetesan-tetesan (droplet) permukaanya memiliki muatan positif, dan masingmasing tetesan (droplet) tidak saling menempel lagi (membentuk tetesan yang lebih besar). Pada
spektra sering terjadi penambahan berat molekul ion-ion tersebut disamping penambahan berat
molekul atau biasanya ditulis dengan [M + molekul ion-ion]. Kemungkinan ion molekul yang
terdeteksi di mass spectroscopy adalah [M + H+], [M - H+], serta analit dengan tambahan seperti
Na+, K+, H3O+, NH4+, dan molekul dari fase gerak ( LC-MS book, Audrey, 2003).