Precursor Chemicals Trends:

U.S. Perspectives
Liqun L. Wong
Unit Chief
Drug & Chemical Evaluation Section
Diversion Control Division
United States Drug Enforcement Administration

U.S. Drug Enforcement Administration 1

 Opioid Health Crisis in U.S.

Total Number of Overdose Deaths, 1999 ‐ 2018
120,000

100,000
 Psychostimulants with abuse potential
 Benzodiazepines
Total Number of Deaths

12,801
 Methadone
80,000  Synthetic Opioids
 Natural and Semisynthetic Opioids 3,040
Cocaine
60,000
 Heroin 31,473

40,000
12,588

20,000 14,762

15,073
0

‐‐ ‐‐ ‐‐ 2018 Provisional data (12‐Month Period Ending on December 2018)
No provisional data for benzodiazepine drug class

U.S. Drug Enforcement Administration 2

 Number of NPS Encounters in U.S.
140,000
Total Number of NPS Drug Reports by Drug Category and Year
96,212
87,094
120,000

Synthetic Cannabinoids
Total Number of Drug Reports

100,000
Synthetic Cathinones
45,882
80,000
Synthetic Opioids
17,968

865 5,769
60,000 1,298
14,998
14,527
16,215 15,715
40,000
744 9,461 10,938
7,209 11,535
20,000 43,197 39,812
34,628 35,980
23,699 29,526 26,350
678 20,233
636 743
29 3,291
0 23
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018*

Source: National Forensic Laboratory Information System (NFLIS), DEA, Queried as of June 12, 2019.  * NFLIS reporting still pending.

U.S. Drug Enforcement Administration 3

 Number of NPS in U.S.

250 Number of Drugs by Category  2009 ‐ 2018*

200 Synthetic Cannabinoids
29 45
Synthetic Cathinones 54
Number of NPS Drugs 

150 Synthetic Opioids 15
9
80
55 75
8 56 69
100 8
39 43
5
50 23
86 93 94 88 81
4 62 67
2 12 44
6 19
0 2
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018*
* NFLIS reporting still pending. 
Source: National Forensic Laboratory Information System (NFLIS), DOE/DC/DEA, Queried as of June 12, 2019

U.S. Drug Enforcement Administration 4

 Fentanyl Clandestine Laboratory -2006

• April 2005 ‐ March 2007: Spike in fentanyl seizures  
• Over 1013 documented non‐pharmaceutical (NPF) overdose deaths
• Primary synthetic route identified as Siegfried method
Fentanyl Fatal Overdose Epidemic, 2005-2007
• N‐phenethyl‐4‐
piperdidone (NPP) 
added as a List 1 
chemical in 2007  
• 4‐anilino‐N‐
phenethyl‐4‐
piperidine (ANPP) 
added as a Schedule 
II immediate 
precursor in 2010
CDC. Nonpharmaceutical fentanyl‐related 
deaths—multiple states, April 2005–March 
2007. MMWR 2008; 57: 793–6.

U.S. Drug Enforcement Administration 5

 Fentanyl Clandestine Laboratory - 2016

ANPP/4‐
ANPP

Seattle, Washington  2016
U.S. Drug Enforcement Administration 6
 Clandestine Pill Press Operation

U.S. Drug Enforcement Administration 7

 Fentanyl Synthesis - Siegfried Route

U.S. Drug Enforcement Administration 8

 Synthetic Opioids in Counterfeit Tablets

U.S. Drug Enforcement Administration 9

 Control of Precursor Chemicals

internationally controlled (CND, 2017)

U.S. Drug Enforcement Administration 11

 Variety of Delivery Methods

cyclopropyl
fentanyl spray

aerosolized acetyl carfentanil on blotter paper

fentanyl

deceased tested
positive
for acetyl fentanyl

U.S. Drug Enforcement Administration 12

 U.S. Fentanyl Signature and Profiling Program

U.S. Drug Enforcement Administration 14

 Analysis of Fentanyl Synthesis
Janssen
O
O O
N H NH N

N
N N N N
H

O O N
N HN
H O N

N
N N N
N
H

NPP ANPP
fentanyl

Diversion Control Division

Siegfried
U.S. Drug Enforcement Administration U.S. Drug Enforcement Administration 15
 Fentanyl Synthesis - Other Methods
Br

HN

H2N
N
H

4-anilinopiperidine (4-AP)
Br
O

O O HN N
O

H2N Cl
N N N N
H
4-piperidone

NPP ANPP fentanyl

U.S. Drug Enforcement Administration 16
 Fentanyl Synthesis – New Precursors

• New method utilizes a substance called 4-AP instead of NPP

• INCB reported 32 notifications (late 2018 - early 2019)
representing 30 kg of 4-AP
• Origins: China, Hong Kong, Netherlands, Singapore, India
• Destination: Mexico

30 kg of 4-AP can
produce 57 kg of
fentanyl!
falsely declared as “foodstuffs or
consumables”, “gifts”, “unspecified
goods”, “glass bottles” and “protein”

U.S. Drug Enforcement Administration 17

 Fentanyl Precursor - Packaging

U.S. Drug Enforcement Administration 18

 Suppliers Help to Evade Customs Detection

“discreet package :the packing suits

you best would be chosen to cross
customs safely. or if you have your
own ideal way, it could be also
taken into consideration .”

“safety guarantee (we do this

business long time ,we know how to
disguise let the product through
customs)”

“our company promise to deliver

clients' package to his hands safely,
or we'll cover the total loss and
reship in time”

U.S. Drug Enforcement Administration 19

 Precursor Chemical Names

From a January 2019 International

Alert Salt form CAS number
Base 23056-29-3
Hydrochloride (1:1) 1193388-65-6
Hydrobromide (1:1) 24775-80-2
Hydrobromide (1:2) 24998-99-0
4-methylbenzenesulfonate (1:?) 918535-64-5
Hydrochloride (1:2) 99918-43-1

U.S. Drug Enforcement Administration 20

 Precursor Chemical – CAS Numbers

Salt form CAS number

Base 23056-29-3
Hydrochloride (1:1) 1193388-65-6
Hydrobromide (1:1) 24775-80-2
Hydrobromide (1:2) 24998-99-0
4-methylbenzenesulfonate (1:?) 918535-64-5
Hydrochloride (1:2) 99918-43-1

U.S. Drug Enforcement Administration 21

 Internet Sales - Precursor Chemicals

22
Diversion Control Division
U.S. Drug Enforcement Administration U.S. Drug Enforcement Administration 22
 Heibei Guanlang Biotechnology (Crovellbio)

• All products have a connection to

drug trade
• Designer precursors
• Cutting agents
• Non-controlled solvents
• Product offerings evolve re:
chemical controls
• Pervasive online presence
• Marking materials reference a
“Mexico Branch”
• Only one of many of examples…

U.S. Drug Enforcement Administration 23

 Designer Precursor Chemicals

CAS number: 125541‐22‐2
U.S. Drug Enforcement Administration 24
 Designer Precursor Chemicals

U.S. Drug Enforcement Administration 25

 Methamphetamine Designer Precursor Chemicals

N
O NH2 MAPA
O O methyl 3-oxo-2-phenylbutanoate
methyl alpha-acetylphenylacetate
3-oxo-2-phenylbutanamide 3-oxo-2-phenylbutanenitrile CAS 16648-44-5
APAA APAAN
4433-77-6 4468-48-8

O O

O O

methyl 3-oxo-2-phenylbutanoate 1-phenylpropan-2-one

MAPA BMK / P-2-P
16648-44-5 103-79-7
O OH

O O

O
3-oxo-2-phenylbutanoic acid ethyl 3-oxo-4-phenylbutanoate
4433-88-9 718-08-1

U.S. Drug Enforcement Administration 26

 INCB on “Designer” Precursor Chemicals

“designer” precursor: A close chemical relative of a controlled precursor that is purpose-made to

circumvent controls and usually does not have any recognized legitimate use.

 Established in 2013, in response to the proliferation of “designer” precursors

 The list currently contains 53 individual substances
 Expanded the list in a generic manner
 ISSL and definitions cover:
 esters and other simple derivatives
 Stable chemical intermediates,
 Purpose-made chemical intermediates
 Masked derivatives of controlled precursors
 others

U.S. Drug Enforcement Administration 27

 Contact Information

Liqun L. Wong
[email protected]
+1-202-307-7183
U.S. Drug Enforcement Administration
www.deadiversion.usdoj.gov

U.S. Drug Enforcement Administration 28