Presentation at Emerald Scientific Conference 2019. We present our work on building an in-process analytical method for cannabinoid quantification by IR for cannabis extract to track decarboxylation. Finding the endpoint is important for process efficiency, but surprisingly difficult. Therefore having a reliable quick and cheap tool to do so is of high value.

1. Optimization of the
Decarboxylation Reaction in
Cannabis Extract
Ariel Bohman, Doug Townsend
PerkinElmer Inc.
&
Dr. Markus Roggen
Complex Biotech Discovery Ventures

2. Cannabis extracts are not new…
• Used extensively
throughout history for
cultural, religious and
medicinal purposes
• Ancient Egypt
• China
• India

3. Concentrates may surpass flower as
the #1 product in the US
2017 2022
Flower
Concentrates
Edibles
Other
Source: Arcview & BDS Analytics Cannabis Intelligence Briefing

4. There is a dizzying array of products
available and various extraction methods
• Bubble hash
• Rosin
• Shatter
• Wax
• Distillate
• Isolate

5. Decarboxylation is one of the most
critical processing steps
CO2
Heat
THCA THC

6. How do you
decarboxylate?

7. How do you decarboxylate?

8. How do you decarboxylate?
Thou shall heat for 7
minutes at 300˚C

9. How do you decarboxylate?
There is a lack of universal agreement
regarding reaction conditions
• Oven heating
• Hot plate
• Microwave
• Oil bath
• Other?

10. How do you decarboxylate?
The producer faces multiple problems over-
compensating with excess heating
• Availability of instruments
• Higher costs of production
• Side reaction and degradation
• Lower yields

11. 0
10
20
30
40
50
60
70
80
0
0.5
1
1.5
2
2.5
3
3.5
0 1000 2000 3000 4000 5000 6000
THC
THC(%)
CBN&d8-THC(%)
d8-THC
CBN
Elapsed Time (Minutes)
How do you decarboxylate?

12. Decarboxylation is rarely monitored
in-process
• Subjective determination of reaction completeness
• Reactionary approach
• Inconsistent batches
• Lack of quality & process control

13. What kind of in-process
testing do you perform?

14. What kind of in-process testing
can we do?
• The ideal technique would be…
Rapid
Zero sample
prep
Small
sample
volumeAccurate
Simple

15. Infrared spectroscopy is a useful tool for
cannabis extractors
Visible
UV
X-rays
Gamma
Infrared
Microwaves
Radio
Wavelength Wavenumber
λ (µm) 𝝊 (cm-1)
NIR 0.78 – 2.5 12800 – 4000
MIR 2.5 – 50 4000 – 200
FIR 50 – 100 200 – 10

16. What does the infrared spectrum
tell us?
Chemical Bonds

17. BG62-64 T0
BG62-64 T80
Name
Sample 023 By Administrator Date Thursday, July 12 2018
Sample 041 By Administrator Date Thursday, July 12 2018
Description
1750 8001600 1400 1200 1000
0.23
-0.01
-0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
0.22
cm-1
A
Start THCA
20.87 %
End THCA
1.56 %
The infrared spectrum can be thought
of as an immediate potency update

18. Sample Preparation
• Milled to 2 mm particle size
• Supercritical CO2 extract
• 20L, 2000 psi system
Apeks Supercritical
Decarboxylation
• 100 g of unprocessed extract
• Hot oil bath, 140 – 150˚C
• Overhead stirring
Sampling
• FTIR sampling every 5 min
• HPLC reference ~ every 15min
Can we quantify decarboxylation in real-
time?

19. Principal Component Regression
• Breakdown spectral dataset into
principal components or factors
• Represent variation within the dataset
• Correlate spectral features to property
value of interest
• Computed such that the first principal
component represents the largest
amount of variance

20. Monitoring THCA in-process…
0
5
10
15
20
25
30
35
0 10 20 30 40 50 60 70 80
THCA(%)
Elapsed Time (Minutes)

21. Monitoring THCA in-process…
0
5
10
15
20
25
30
35
0 10 20 30 40 50 60 70 80
THCA(%)
Elapsed Time (Minutes)

22. 16
26
36
46
56
66
76
16 26 36 46 56 66 76
Predicted%THC
Reference % THC
5 PCs
R2 = 0.998
CV-SEP = 1.6 %
IR was calibrated with HPLC data

23. Infrared spectroscopy is a powerful
tool for cannabis extractors
0
5
10
15
20
25
30
35
0 10 20 30 40 50 60 70 80
THCA(%)
Elapsed Time (Minutes)

24. How do you
decarboxylate?
What in-process testing
do you perform?

25. Thank you!
Ariel Bohman
Ariel.Bohman@PERKINELMER.COM
&
Dr. Markus Roggen
markus@cbdvl.com

26. How can this be used?
Optimization
Precision
Decarboxylation

29. IR was calibrated with HPLC data
0
5
10
15
20
25
30
35
0 5 10 15 20 25 30 35
Predicted%THCA
Reference % THCA
4 PCs
R2 = 0.989
CV-SEP = 1.8 %

30. Monitoring THC in-process…
0
10
20
30
40
50
60
0 10 20 30 40 50 60 70 80 90
THC(%)
Elapsed Time (Minutes)

31. Monitoring THC in-process…
0
10
20
30
40
50
60
0 10 20 30 40 50 60 70 80 90
THC(%)
Elapsed Time (Minutes)