scholarly journals Identification of Recent Cannabis Use: Whole-Blood and Plasma Free and Glucuronidated Cannabinoid Pharmacokinetics following Controlled Smoked Cannabis Administration

2011 ◽  
Vol 57 (10) ◽  
pp. 1406-1414 ◽  
Author(s):  
David M Schwope ◽  
Erin L Karschner ◽  
David A Gorelick ◽  
Marilyn A Huestis

BACKGROUND Δ9-Tetrahydrocannabinol (THC) is the most frequently observed illicit drug in investigations of accidents and driving under the influence of drugs. THC-glucuronide has been suggested as a marker of recent cannabis use, but there are no blood data following controlled THC administration to test this hypothesis. Furthermore, there are no studies directly examining whole-blood cannabinoid pharmacokinetics, although this matrix is often the only available specimen. METHODS Participants (9 men, 1 woman) resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. We quantified THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide and THCCOOH-glucuronide directly in whole blood and plasma by liquid chromatography/tandem mass spectrometry within 24 h of collection to obviate stability issues. RESULTS Median whole blood (plasma) observed maximum concentrations (Cmax) were 50 (76), 6.4 (10), 41 (67), 1.3 (2.0), 2.4 (3.6), 89 (190), and 0.7 (1.4) μg/L 0.25 h after starting smoking for THC, 11-OH- THC, THCCOOH, CBD, CBN, and THCCOOH-glucuronide, respectively, and 0.5 h for THC-glucuronide. At observed Cmax, whole-blood (plasma) detection rates were 60% (80%), 80% (90%), and 50% (80%) for CBD, CBN, and THC-glucuronide, respectively. CBD and CBN were not detectable after 1 h in either matrix (LOQ 1.0 μg/L). CONCLUSIONS Human whole-blood cannabinoid data following cannabis smoking will assist whole blood and plasma cannabinoid interpretation, while furthering identification of recent cannabis intake.

2009 ◽  
Vol 55 (6) ◽  
pp. 1188-1195 ◽  
Author(s):  
Eugene W Schwilke ◽  
Erin L Karschner ◽  
Ross H Lowe ◽  
Ann M Gordon ◽  
Jean Lud Cadet ◽  
...  

Abstract Background: Whole-blood concentrations of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) are approximately half of those in plasma due to high plasma protein binding and poor cannabinoid distribution into erythrocytes. Whole blood is frequently the only specimen available in forensic investigations; controlled cannabinoid administration studies provide scientific data for interpretation of cannabinoid tests but usually report plasma concentrations. Whole-blood/plasma cannabinoid ratios from simultaneously collected authentic specimens are rarely reported. Methods: We collected whole blood for 7 days from 32 individuals residing on a closed research unit. Part of the whole blood was processed to obtain plasma, and the whole blood and plasma were stored at −20 °C until analysis by validated 2-dimensional GC-MS methods. Results: We measured whole-blood/plasma cannabinoid ratios in 187 specimen pairs. Median (interquartile range) whole-blood/plasma ratios were 0.39 (0.28–0.48) for THC (n = 75), 0.56 (0.43–0.73) for 11-OH-THC (n = 17), and 0.37 (0.24–0.56) for THCCOOH (n = 187). Intrasubject variability was determined for the first time: 18.1%–56.6% CV (THC) and 10.8%–38.2% CV (THCCOOH). The mean whole-blood/plasma THC ratio was significantly lower than the THCCOOH ratio (P = 0.0001; 4 participants’ mean THCCOOH ratios were >0.8). Conclusions: Intra- and intersubject whole-blood/plasma THC and THCCOOH ratios will aid interpretation of whole-blood cannabinoid data.


2011 ◽  
Vol 57 (8) ◽  
pp. 1127-1136 ◽  
Author(s):  
Dayong Lee ◽  
Garry Milman ◽  
Allan J Barnes ◽  
Robert S Goodwin ◽  
Jussi Hirvonen ◽  
...  

BACKGROUND Oral fluid (OF) is an accepted alternative biological matrix for drug treatment, workplace, and DUID (driving under the influence of drugs) investigations, but establishing the cannabinoid OF detection window and concentration cutoff criteria are important. METHODS Cannabinoid concentrations were quantified in OF from chronic, daily cannabis smokers during monitored abstinence. Δ9-tetrahydrocannabinol (THC)3, cannabidiol (CBD), cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) were determined in daily OF samples collected with the Quantisal™ device. GC-MS limits of quantification (LOQ) were 0.5 μg/L for THC and CBD, 1 μg/L for CBN, and 7.5 ng/L for THCCOOH. RESULTS After providing written informed consent for this institutional review board–approved study, 28 participants resided from 4 to 33 days on the secure research unit and provided 577 OF specimens. At the LOQ, THC was generally quantifiable for 48 h, whereas CBD and CBN were detected only at admission. Median THCCOOH detection time was 13 days (CI 6.4–19.6 days). Mean THC detection rates decreased from 89.3% at admission to 17.9% after 48 h, whereas THCCOOH gradually decreased from 89.3% to 64.3% within 4 days. Criteria of THC ≥2 μg/L and THCCOOH ≥20 ng/L reduced detection to <48 h in chronic cannabis smokers. An OF THCCOOH/THC ratio ≤4 ng/μg or presence of CBD or CBN may indicate more recent smoking. CONCLUSIONS THC, THCCOOH, CBD, and CBN quantification in confirmatory OF cannabinoid testing is recommended. Inclusion of multiple cannabinoid cutoffs accounted for residual cannabinoid excretion in OF from chronic, daily cannabis smokers and could reduce the potential for positive test results from passive cannabis smoke exposure and lead to greatly improved test interpretation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michele Dei Cas ◽  
Jessica Rizzo ◽  
Mariangela Scavone ◽  
Eti Femia ◽  
Gian Marco Podda ◽  
...  

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.


1998 ◽  
Vol 236 (1-2) ◽  
pp. 29-34 ◽  
Author(s):  
M. M. Mason ◽  
J. S. Morris ◽  
V. L. Spate ◽  
C. K. Baskett ◽  
T. A. Nichols ◽  
...  

1980 ◽  
Vol 186 (2) ◽  
pp. 591-598 ◽  
Author(s):  
Christopher Kirby ◽  
Jacqui Clarke ◽  
Gregory Gregoriadis

Small unilamellar neutral, negatively and positively charged liposomes composed of egg phosphatidylcholine, various amounts of cholesterol and, when appropriate, phosphatidic acid or stearylamine and containing 6-carboxyfluorescein were injected into mice, incubated with mouse whole blood, plasma or serum or stored at 4°C. Liposomal stability, i.e. the extent to which 6-carboxyfluorescein is retained by liposomes, was dependent on their cholesterol content. (1) Cholesterol-rich (egg phosphatidylcholine/cholesterol, 7:7 molar ratio) liposomes, regardless of surface charge, remained stable in the blood of intravenously injected animals for up to at least 400min. In addition, stability of cholesterol-rich liposomes was largely maintained in vitro in the presence of whole blood, plasma or serum for at least 90min. (2) Cholesterol-poor (egg phosphatidylcholine/cholesterol, 7:2 molar ratio) or cholesterol-free (egg phosphatidylcholine) liposomes lost very rapidly (at most within 2min) much of their stability after intravenous injection or upon contact with whole blood, plasma or serum. Whole blood and to some extent plasma were less detrimental to stability than was serum. (3) After intraperitoneal injection, neutral cholesterol-rich liposomes survived in the peritoneal cavity to enter the blood circulation in their intact form. Liposomes injected intramuscularly also entered the circulation, although with somewhat diminished stability. (4) Stability of neutral and negatively charged cholesterol-rich liposomes stored at 4°C was maintained for several days, and by 53 days it had declined only moderately. Stored liposomes retained their unilamellar structure and their ability to remain stable in the blood after intravenous injection. (5) Control of liposomal stability by adjusting their cholesterol content may help in the design of liposomes for effective use in biological systems in vivo and in vitro.


2010 ◽  
Vol 109 (1-3) ◽  
pp. 243-247 ◽  
Author(s):  
Marleen M.H.J. van Gelder ◽  
Jennita Reefhuis ◽  
Alissa R. Caton ◽  
Martha M. Werler ◽  
Charlotte M. Druschel ◽  
...  

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