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Quantification of cocaine and metabolites in exhaled breath by liquid chromatography-high-resolution mass spectrometry following controlled administration of intravenous cocaine

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Abstract

Breath has been investigated as an alternative matrix for detecting recent cocaine intake; however, there are no controlled cocaine administration studies that investigated the drug’s disposition into breath. Breath was collected from 10 healthy adult cocaine users by asking them to breathe into a SensAbues device for 3 min before and up to 22 h following 25 mg intravenous (IV) cocaine dosing on days 1, 5, and 10, and assayed with a validated liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method to quantify breath cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine. The assay was linear from 25 to 1,000 pg/filter, extraction efficiencies were 83.6–126 %, intra- and inter-assay imprecision was <10.6 %, and bias was between −8.5 and 16.8 %. No endogenous or exogenous interferences were observed for more than 75 tested. Analytes were generally stable under short-term storage conditions. Ion suppression was less than 46 %. Of breath specimens collected after controlled cocaine administration, 2.6 % were positive for cocaine (26.1–66 pg/filter, 1–9.5 h), 0.72 % BE (83.3–151 pg/filter, 6.5–12.5 h), and 0.72 % EME (50–69.1 pg/filter, 6.5–12.5 h); norcocaine was not detected. Methanolic extraction of the devices themselves, after filters were removed, yielded 19.2 % positive cocaine tests (25.2–36.4 pg/device, 10 min–22 h) and 4.3 % positive BE tests (26.4–93.7 pg/device, 10 min–22 h), explaining differences between the two extraction techniques. These results suggest that the device reflects the drug in oral fluid as well as lung microparticles, while the filter reflects only drug-laden microparticles. A sensitive and specific method for cocaine, BE, EME, and norcocaine quantification in breath was developed and validated. Cocaine in breath identifies recent cocaine ingestion, but its absence does not preclude recent use.

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Acknowledgments

This work was supported by the Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH). The authors acknowledge the contributions of the clinical staff of the NIDA-IRP and the Clinical Research Unit, Johns Hopkins Bayview Medical Center, as well as the University of Maryland, Baltimore, a member of the Graduate Partnership Program, NIH.

Conflict of interest

O. Beck has part ownership in SensAbues producing the sampling devices (O. Beck, US patent number 13/394,609).

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Authors and Affiliations

  1. Chemistry and Drug Metabolism, National Institute on Drug Abuse, NIH, Baltimore, MD, 21224, USA

    Kayla N. Ellefsen, Marta Concheiro, Sandrine Pirard & Marilyn A. Huestis

  2. Program in Toxicology, University of Maryland, Baltimore, Baltimore, MD, 21201, USA

    Kayla N. Ellefsen

  3. Karolinska Institute, 17177, Stockholm, Sweden

    Olof Beck

  4. Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, MD, 21224, USA

    David A. Gorelick

Authors
  1. Kayla N. Ellefsen
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  2. Marta Concheiro
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  3. Olof Beck
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  4. David A. Gorelick
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  5. Sandrine Pirard
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  6. Marilyn A. Huestis
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Corresponding author

Correspondence to Marilyn A. Huestis.

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Ellefsen, K.N., Concheiro, M., Beck, O. et al. Quantification of cocaine and metabolites in exhaled breath by liquid chromatography-high-resolution mass spectrometry following controlled administration of intravenous cocaine. Anal Bioanal Chem 406, 6213–6223 (2014). https://doi.org/10.1007/s00216-014-8051-x

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  • DOI: https://doi.org/10.1007/s00216-014-8051-x

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