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Direct quantification of cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography–tandem mass spectrometry

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Abstract

The first method for quantifying cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed and validated. Solid-phase extraction followed protein precipitation with acetonitrile. High-performance liquid chromatography separation was achieved in 16 min via gradient elution. Electrospray ionization was utilized for cannabinoid detection; both positive (Δ9-tetrahydrocannabinol [THC] and cannabinol [CBN]) and negative (11-hydroxy-THC [11-OH-THC], 11-nor-9-carboxy-THC [THCCOOH], cannabidiol [CBD], THC-glucuronide, and THCCOOH-glucuronide) polarity were employed with multiple reaction monitoring. Calibration by linear regression analysis utilized deuterium-labeled internal standards and a 1/x 2 weighting factor, yielding R 2 values >0.997 for all analytes. Linearity ranged from 0.5 to 50 μg/L (THC-glucuronide), 1.0–100 μg/L (THC, 11-OH-THC, THCCOOH, CBD, and CBN), and 5.0–250 μg/L (THCCOOH-glucuronide). Imprecision was <10.5% CV, recovery was >50.5%, and bias within ±13.1% of target for all analytes at three concentrations across the linear range. No carryover and endogenous or exogenous interferences were observed. This new analytical method should be useful for quantifying cannabinoids in whole blood and further investigating cannabinoid glucuronides as markers of recent cannabis intake.

LC–MS/MS MRM ion chromatograms of extracted blank whole blood and cannabinoid analytes at limits of quantification

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Acknowledgements

The authors thank Allan Barnes, Erin Karschner, Teresa Gray, Amanda Rigdon, and the clinical staff of the NIDA Intramural Research Program for technical assistance. This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health.

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Authors and Affiliations

  1. Chemistry and Drug Metabolism, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA

    David M. Schwope, Karl B. Scheidweiler & Marilyn A. Huestis

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  1. David M. Schwope
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  2. Karl B. Scheidweiler
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  3. Marilyn A. Huestis
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Correspondence to Marilyn A. Huestis.

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Schwope, D.M., Scheidweiler, K.B. & Huestis, M.A. Direct quantification of cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 401, 1273–1283 (2011). https://doi.org/10.1007/s00216-011-5197-7

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  • DOI: https://doi.org/10.1007/s00216-011-5197-7

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