Assessment of the Utility of the Oral Fluid and Plasma Proteomes for Hydrocodone Exposure

  • Brooke L. Deatherage Kaiser
  • Jon M. Jacobs
  • Athena A. Schepmoes
  • Heather M. Brewer
  • Bobbie-Jo M. Webb-Robertson
  • Sandra Valtier
  • Vikhyat S. BebartaEmail author
  • Joshua N. Adkins
Original Article



Non-medical use and abuse of prescription opioids is a growing problem in both the civilian and military communities, with minimal technologies for detecting hydrocodone use. This study explored the proteomic changes that occur in the oral fluid and blood plasma following controlled hydrocodone administration in 20 subjects.


The global proteomic profile was determined for samples taken at four time points per subject: pre-exposure and 4, 6, or 168 hours post-exposure. The oral fluid samples analyzed herein provided greater differentiation between baseline and response time points than was observed with blood plasma, at least partially due to significant person-to-person relative variability in the plasma proteome.


A total of 399 proteins were identified from oral fluid samples, and the abundance of 118 of those proteins was determined to be significantly different upon metabolism of hydrocodone (4 and 6 hour time points) as compared to baseline levels in the oral fluid (pre-dose and 168 hours).


We present an assessment of the oral fluid and plasma proteome following hydrocodone administration, which demonstrates the potential of oral fluid as a noninvasive sample that may reveal features of hydrocodone in opioid use, and with additional study, may be useful for other opioids and in settings of misuse.


Oral fluid Hydrocodone Proteomics Opioid Plasma 



Work was performed in the Environmental Molecular Sciences Laboratory, a US Department of Energy Office of Biological and Environmental Research national scientific user facility located at the Pacific Northwest National Laboratory in Richland, Washington. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy under Contract No. DE-AC05-76RLO 1830. Many thanks to Robert Mueck for sample processing and metabolic profiling analysis. The opinions represented in this manuscript do not necessarily represent the views and opinions of the US Government, Department of Defense, or US Air Force.

Funding Information

Funding was provided by the DoD (Department of Defense) CDMRP (Congressionally Directed Medical Research Program) W81WXH-11-2-0126.

Compliance with Ethical Standards

The study was approved by the Wilford Hall Medical Center and Pacific Northwest National Laboratory Institutional Review Boards.

Conflict of Interest


Supplementary material

13181_2019_731_Fig3_ESM.png (165 kb)
Fig. S1.

Principal Component Analysis of the Blood Plasma Proteome Following Hydrocodone Administration. Principal Component Analysis (PCA) was used to visualize the relatedness of protein observations from blood plasma samples. Blood plasma proteome data demonstrated greater similarity by individual than by time post hydrocodone exposure. This is demonstrated by clustering of individuals (represented by varying colors) and not by time point post-drug administration. PC1 (x-axis) is principal component 1 and PC2 (y-axis) is principal component 2; PC1 and PC2 are the two principal components that account for the most variability in the data, with PC1 being the greatest. Percentages shown are the percent of variability that each PC accounts for. (PNG 164 kb)

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High resolution image (TIF 221 kb)
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Supplementary Table 1 (PDF 38 kb)
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Supplementary Table 2 (PDF 343 kb)
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Supplementary Table 3 (PDF 1135 kb)
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Supplementary Table 4 (PDF 53 kb)


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Copyright information

© American College of Medical Toxicology 2019

Authors and Affiliations

  1. 1.Chemical and Biological Signature Sciences GroupPacific Northwest National LaboratoryRichlandUSA
  2. 2.Biological Sciences DivisionPacific Northwest National LaboratoryRichlandUSA
  3. 3.Environmental Molecular Sciences LaboratoryPacific Northwest National LaboratoryRichlandUSA
  4. 4.Science and TechnologySan AntonioUSA
  5. 5.University of Colorado School of MedicineAuroraUSA

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