Building the Chemical Foundation 

for Intelligent Breath Analysis

K. Jeerage, M. Harries, C. Suiter, E. Holland, J. Widegren, T. Lovestead

Fluid Characterization Group

Applied Chemicals & Materials Division, NIST-Boulder

Funding: NIST Special Programs Office
Drug Sampling Options

Blood Sample

1.5 h – 4 h delay
Breath Sample

Drug Sampling Options

O2

CO2

N2

H2O 

Ar

Ethanol

0.4 mg / liter breath

at legal limit
Ethanol

Cannabis

Known correlation between conc. and impairment

Blood-breath ratio ≈ 2350 (mean)

Simple elimination profile; not stored in fat tissue

Unknown correlation between conc. and impairment

Unknown elimination profile; stored in fat tissue

Thermophysical properties – known

Blood-breath ratio ≈

Thermophysical properties – unknown and difficult to measure

?
Cannabis is Challenging

C21H30O2

C2H5OH

∆-9-tetrahydrocannabinol (THC)

ethanol

terpenes

metabolites

cannabigerol & cannabinol
Cannabis is Challenging

C21H30O2

C2H5OH
Properties for Reliable Quantitation

FAT BLOOD BREATH SORBENT

Partitioning

Vapor Pressure

[A]AIR

KB/A = 

[A]BLOOD

[A]BLOOD

KF/B = 

[A]FAT

[A]AIR

KS/A = 

[A]PDMS
PSAT – Standard Method

Mononitrotoluene taggants

Widegren et al. J. Chem. Eng. Data 55, 2010.

Low-volatility terpenes

Widegren et al. Environ. Sci. Technol. 44, 2010.

Internal eicosane control 

Widegren et al. Fuel 90, 2011

Influence of carrier gas

Widegren et al. J. Chem. Eng. Data 60, 2015.

Anti-oxidants for unstable chemicals

Widegren et al. J. Chem. Eng. Data 62, 2017.

Time = 1 – 8 weeks

Concatenated Gas Saturation

30 °C – 90 ° C

ca. 20 °C

SATURATORSATURATOR

ADSORBERADSORBER
Time = 1 – 2 hours

PSAT – Rapid Method

Porous Layer Open Tubular 

(PLOT) Cryoadsorption

10

8

6

4

2

0

2.6 2.8 3.0 3.2 3.4

1000 / T(K)

ln[PSAT(Pa)103]

30 °C

Eicosane (C20H42)

282.5 g/mol

Tetradecane validation

Lovestead et al. Anal. Chem. 82, 2010.

Cannabinoids

Lovestead et al. Forensic Chem. 5, 2017.

SATURATOR

ADSORBER

30 °C – 300 °C

-10 °C
PSAT – Rapid Method

THC: 0.000115 Pa @ 40 °C

2.3 2.5 2.7 2.9 3.1

1000 / T(K)

8

6

4

2

0

ln[PSAT(Pa)104]

10

THC (C21H30O2)

60 °C

314 g/mol

Time = 1 – 2 hours

Porous Layer Open Tubular 

(PLOT) Cryoadsorption SATURATOR ADSORBER

30 °C – 300 °C

-10 °C
PSAT – Rapid Method

THC: 0.000115 Pa @ 40 °C

2.3 2.5 2.7 2.9 3.1

1000 / T(K)

8

6

4

2

0

ln[PSAT(Pa)104]

10

THC (C21H30O2)

60 °C

314 g/mol

Time = 1 – 2 hours

Porous Layer Open Tubular 

(PLOT) Cryoadsorption SATURATOR ADSORBER

30 °C – 300 °C

-10 °C

Ethanol: 18,000 Pa @ 40 °C

SOURCE: NIST REFPROP Database
KBlood/Air – PLOT Cryoadsorption Method

Can we capture and concentrate sufficient material 

at physiological temperatures?

How does ethanol impact blood/air partitioning?

TEMP: 30 °C – 40 °C

Sample = Mixture

human blood with cannabinoids 

or terpenes

Capture = Multiple Components

water may compete for 

adsorption sites

CARRIER GAS
Octanol + D2O

KFat/Blood – Non-Invasive NMR Method

1H Chemical Shift 

Eugenol in 

Octanol + D2O

Eugenol in D2O

Fat Surrogate = Octanol

Blood Surrogate = Water Eugenol 

Signals

Octanol 

Signals
KPDMS/AIR – Model Feasibility

Capillary Microextraction of Volatiles (CMV)

SPME Fiber

Is it feasible to predict sorbent-air partitioning 

with an empirical model?

Partition Coefficient

PDMS Structure

Synthetic Designer Drugs
KPDMS/AIR – Chemicals for Model

1) Log K at three temperatures: 60 °C - 180 ° C

2) Follows van’t Hoff Equation with R2 > 0.95

Training Set Requirements

Functional Groups (18)

Non-Ring Groups

>C<

>CH-

-CH2-

-CH3

=C<

=CH-

=CH2

Ring Groups

>C<

>CH-

-CH2-

=C<

=CHOxygen Groups

-OH (alcohol)

-OH (phenol)

-O-

>C=O

-CHO

-COO-
KPDMS/AIR – Model Evaluation

K. Jeerage et al. 20th Symposium on Thermophysical Properties, June 2018.

Compare experimental values (x axis) with predicted values 

(y axis) for chemicals used to build model (N = 275).
KPDMS/AIR – Model Predictions 

Predict values for chemicals not used to build model.

K. Jeerage et al. J. Breath Res. (in preparation)

Example: C8 chemicals at 100 °C

Experimental Data

Model Prediction

% Difference
Summary

Outreach: ASTM Committee D37 on Cannabis, Front Range Forensic Chemists

Association, Colorado Bureau of Investigation, Cannabis Industry

Current Partnerships: Prof. Jerry King (University of Arkansas), Prof. Roger

Giese (Northeastern University), Prof. April Hill (Metro State University), Prof.

Lupita Montoya (University of Colorado)

Quantitative breath analysis of cannabinoids will

be challenging due to their low volatility and their

low concentration in blood.

Thermophysical property measurements for large,

hydrophobic, low-volatility chemicals push the

limits of existing experimental approaches.
Boulder Cannabis Research Team

Chris L. Suiter

Megan E. Harries Kavita M. Jeerage Tara M. Lovestead

Jason A. Widegren

Please contact any of us to discuss working together 

or to discuss postdoctoral opportunities.

jeerage@boulder.nist.gov