Kayla N Ellefsen1, Marta Concheiro2, Sandrine Pirard3, David A Gorelick4, Marilyn A Huestis5. 1. Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States; Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, United States. 2. Currently Department of Sciences, John Jay College of Criminal Justice, City University of New York, New York, NY, United States. 3. University of Maryland Health Center, College Park, MD, United States. 4. Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States. 5. Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, United States. Electronic address: marilyn.huestis@gmail.com.
Abstract
BACKGROUND: No controlled cocaine administration data describe cocaine and metabolite disposition in oral fluid (OF) collected with commercially-available collection devices, OF-plasma ratios, and pharmacodynamic relationships with plasma and OF cocaine and metabolite concentrations. METHODS: Eleven healthy, cocaine-using adults received 25mg intravenous cocaine. Physiological and subjective effects (visual analogue scales), and plasma were collected one hour prior, and up to 21h post-dose. OF was collected with the Quantisal™ device up to 69h post-dose. Cocaine, benzoylecgonine (BE) and ecgonine methyl ester were quantified in plasma by liquid chromatography-tandem mass spectrometry; cocaine and BE were quantified in OF by two dimensional-gas chromatography-mass spectrometry. RESULTS: Increases in heart rate, blood pressure and positive subjective effects occurred within the first 15min, persisting up to 1h ("Rush"), with clockwise hysteresis observed for plasma and OF concentrations and some subjective measures. Peak subjective effects ("Rush," "Good drug effect" and "Bad drug effect") occurred prior to peak OF cocaine concentration, whereas observed peak plasma concentrations and subjective measures occurred simultaneously, most likely due to significantly earlier plasma Tmax compared to OF Tmax.Tlast was generally longer in OF (12.5h cocaine; 33.0h BE) than plasma (9.5h cocaine; >21h BE, cutoffs 1μg/L); 8 and 10μg/L OF cocaine confirmatory cutoffs yielded detection times similar to cocaine's impairing effects, suggesting usefulness for DUID testing. CONCLUSIONS: OF offers advantages as an alternative matrix to blood and plasma for identifying cocaine intake, defining pharmacokinetic parameters at different confirmation cutoffs, and aiding different drug testing programs to best achieve their monitoring goals.
BACKGROUND: No controlled cocaine administration data describe cocaine and metabolite disposition in oral fluid (OF) collected with commercially-available collection devices, OF-plasma ratios, and pharmacodynamic relationships with plasma and OF cocaine and metabolite concentrations. METHODS: Eleven healthy, cocaine-using adults received 25mg intravenous cocaine. Physiological and subjective effects (visual analogue scales), and plasma were collected one hour prior, and up to 21h post-dose. OF was collected with the Quantisal™ device up to 69h post-dose. Cocaine, benzoylecgonine (BE) and ecgonine methyl ester were quantified in plasma by liquid chromatography-tandem mass spectrometry; cocaine and BE were quantified in OF by two dimensional-gas chromatography-mass spectrometry. RESULTS: Increases in heart rate, blood pressure and positive subjective effects occurred within the first 15min, persisting up to 1h ("Rush"), with clockwise hysteresis observed for plasma and OF concentrations and some subjective measures. Peak subjective effects ("Rush," "Good drug effect" and "Bad drug effect") occurred prior to peak OF cocaine concentration, whereas observed peak plasma concentrations and subjective measures occurred simultaneously, most likely due to significantly earlier plasma Tmax compared to OF Tmax.Tlast was generally longer in OF (12.5h cocaine; 33.0h BE) than plasma (9.5h cocaine; >21h BE, cutoffs 1μg/L); 8 and 10μg/L OF cocaine confirmatory cutoffs yielded detection times similar to cocaine's impairing effects, suggesting usefulness for DUID testing. CONCLUSIONS: OF offers advantages as an alternative matrix to blood and plasma for identifying cocaine intake, defining pharmacokinetic parameters at different confirmation cutoffs, and aiding different drug testing programs to best achieve their monitoring goals.
Authors: Aidan J Hampson; Jennifer R Schroeder; Kayla N Ellefsen; Luba Yammine; David H Epstein; Kenzie L Preston; Marilyn A Huestis; Christopher D Verrico Journal: Clin Pharmacol Ther Date: 2020-07-11 Impact factor: 6.875
Authors: Sofia Bouhlal; Kayla N Ellefsen; Mikela B Sheskier; Erick Singley; Sandrine Pirard; David A Gorelick; Marilyn A Huestis; Lorenzo Leggio Journal: Drug Alcohol Depend Date: 2017-08-31 Impact factor: 4.492
Authors: Francisco Herrera-Gómez; Eduardo Gutiérrez-Abejón; Mercedes García-Mingo; F Javier Álvarez Journal: Int J Environ Res Public Health Date: 2021-05-18 Impact factor: 3.390