Robust analytical method for e-cigarette PMTA guidance analyte: propionic acid 2021_ST22_ZhuJeff.pdf

1. Analysis of Organic Acids in E-Vapor Products
by Ion Chromatography
ZHU J.*; SNEAD E.; HAGERTY G.
ITG Brands, LLC, Greensboro, NC, USA
CORESTA SSPT2021
*Email: jeff.zhu@itgbrands.com
2021_ST22_ZhuJeff.pdf
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2. Introduction
• Organic acids (formic acid, acetic acid, propionic acid and lactic acid)
are of interest for e-vapor products testing, especially propionic acid
which is included in guidance from FDA-CTP1.
• Here we present a simple and low-cost method for the analysis of
these organic acids in E-vapor aerosols and e-liquids by ion
chromatography.
1) No derivatization needed – “shake and shoot”.
2) Use DI water as extraction solution and mobile phase (with KOH)
– no organic solvent required for the method.
1) Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems - Guidance for
Industry, FDA Center for Tobacco Products, June 2019.
2021_ST22_ZhuJeff.pdf
SSPT2021
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not
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CORESTA

3. Method – Instrument
IC Instruments: Thermo ICS 5000 or ICS 6000
Column: Dionex IonPac AS11-HC-4μm Analytical Column 2 x 250 mm
Column temperature: 30 °C
Flow rate: 0.35 mL/min
Mobile phase : KOH in DI water (Gradient see table below)
Time (min) KOH (mM) Curve
0 1.2 5
6 1.2 5
9.9 2.5 5
10 40 5
13.9 40 5
14 1.2 5
19 1.2 5
2021_ST22_ZhuJeff.pdf
SSPT2021
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4. Method – Instrument
Autosampler temperature: set at 4 °C
Injection volume: 6 µL
Suppressor: ADRS600, 2 mm
Suppressor current: 35 mA
Detector cell temperature: 30 °C
Compartment temperature: 23 °C
Total runtime: 19 min
2021_ST22_ZhuJeff.pdf
SSPT2021
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5. Method – Sample Preparation
Aerosol:
After aerosol collection*, transfer the glass fiber filter pad to 50 mL PP vial.
Add 36 mL of DI water into the vial and cap.
Shake on an orbital shaker for 30 minutes at 210 rpm.
Filter the solutions into PP autosampler vials through 0.2 µm PP filters.
E-Liquid:
Follows same process as aerosol using e-liquid instead of pad for extraction and
extraction at 300 rpm instead of 210 rpm.
*: 1) Cerulean SM 450 for ISO 20768, or Cerulean CETI-8 for either ISO 20768 or intense regime.
2) In-house trapping efficiency study shows >99% of analytes are collected in pads vs in impingers.
2021_ST22_ZhuJeff.pdf
SSPT2021
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not
peer-reviewed
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CORESTA

6. Results – Calibration Curves on ICS 5000
- Range: 0.03 to 5 µg/mL
R2 = 0.99995
R2 = 0.99994
R2 = 0.99991
R2 = 0.99984
2021_ST22_ZhuJeff.pdf
SSPT2021
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not
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7. Results – Signal to Noise Ratio
S/N at Low Standard levels
*: to quantitate the concentrations at LOQ spike levels during the validation
Instrument Standards S/N Lactic Acid Acetic Acid Propionic Acid Formic Acid
ICS 5000 Std 1S (0.03 µg/mL)* 30.7 73.8 44.0 92.5
Std 1 (0.05 µg/mL) 41.8 83.2 49.3 107.7
ICS 6000 Std 1S (0.03 µg/mL)* 50.3 65.6 44.9 122.1
Std 1 (0.05 µg/mL) 72.1 102.1 68.8 160.3
2021_ST22_ZhuJeff.pdf
SSPT2021
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not
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8. Results – Standards Accuracies on ICS 5000
*: to quantitate the concentrations at LOQ spike levels during the validation
Standard Lactic Acid Acetic Acid Propionic Acid Formic Acid
Std 1S (0.03 µg/mL)* 103.4% 105.0% 99.6% 99.0%
Std 1 (0.05 µg/mL) 96.0% 100.4% 100.0% 102.1%
Std 2 (0.1 µg/mL) 101.2% 93.2% 97.3% 99.2%
Std 3 (0.2 µg/mL) 99.4% 101.2% 102.7% 100.3%
Std 4 (0.5 µg/mL) 99.1% 98.6% 99.9% 98.2%
Std 5 (1 µg/mL) 101.4% 102.2% 101.4% 101.6%
Std 6 (2.5 µg/mL) 99.5% 99.3% 98.9% 99.6%
Std 7 (5 µg/mL) 100.1% 100.1% 100.2% 100.1%
2021_ST22_ZhuJeff.pdf
SSPT2021
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Document
not
peer-reviewed
by
CORESTA

9. Results – Chromatogram on ICS 5000
- PG/VG/Nic aerosol sample spiked at LOQ Level (0.05 µg/mL)
2021_ST22_ZhuJeff.pdf
SSPT2021
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not
peer-reviewed
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10. Recoveries for Aerosol Samples
*: Puff volume/frequency/duration/profile 95mL/30s/5s/square
Aerosol ISO 20768:2018 Lactic Acid Acetic Acid Propionic Acid Formic Acid
PG/VG/Nic Base Liquid Low Spike 106.0% 104.6% 106.5% 102.9%
Commercial E-Cig 1 Mid Spike 108.7% 105.6% 107.0% 101.1%
Commercial E-Cig 2 Mid Spike 99.3% 105.4% 103.3% 105.3%
Commercial E-Cig 1 High Spike 105.2% 101.0% 100.7% 100.4%
Commercial E-Cig 2 High Spike 109.0% 107.8% 108.3% 108.5%
Aerosol Intense* Lactic Acid Acetic Acid Propionic Acid Formic Acid
PG/VG/Nic Base Liquid Low Spike 104.7% 99.3% 97.0% 102.3%
Commercial E-Cig 1 Mid Spike 105.3% 108.5% 103.3% 103.2%
Commercial E-Cig 1 High Spike 104.8% 104.6% 100.6% 102.7%
2021_ST22_ZhuJeff.pdf
SSPT2021
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Document
not
peer-reviewed
by
CORESTA

11. Recoveries for E-Liquid Samples
E-Liquid Lactic Acid Acetic Acid Propionic Acid Formic Acid
PG/VG/Nic Base Liquid Low Spike 106.0% 92.8% 97.8% 95.7%
Commercial E-Cig 1 Mid Spike 118.8% 104.4% 108.3% 103.4%
Commercial E-Cig 2 Mid Spike 110.9% 112.3% 107.0% 122.8%
Commercial E-Cig 1 High Spike 103.8% 100.7% 105.6% 102.4%
Commercial E-Cig 2 High Spike 112.2% 111.0% 110.2% 108.8%
2021_ST22_ZhuJeff.pdf
SSPT2021
-
Document
not
peer-reviewed
by
CORESTA

12. Conclusions
• We have presented a simple and low-cost method for the analysis of organic
acids in E-vapor aerosols and e-liquids by ion chromatography.
• The method has been validated with good accuracies and is applicable to a
wide range of e-vapor products.
2021_ST22_ZhuJeff.pdf
SSPT2021
-
Document
not
peer-reviewed
by
CORESTA