Charles LoDico

Prescription Opioids. I. Metabolism and Excretion Patterns of Oxycodone in Urine Following Controlled Single Dose Administration

Hydrocodone (HC) is a highly misused prescription drugs in the USA. Interpretation of urine tests for HC is complicated by its metabolism to two metabolites, hydromorphone (HM) and dihydrocodeine (DHC), which are also available commercially and are misused. Currently, there is interest in including HC and HM in the federal workplace drug-testing programs. This study characterized the disposition of HC in human urine. Twelve healthy, drug-free, adults were administered a single, oral 20 mg immediate-release dose of HC in a controlled clinical setting. Urine specimens were collected at timed intervals for up to 52 h and analyzed by LC-MS-MS (limit of quantitation = 50 ng/mL) with and without enzymatic hydrolysis. All specimens were also analyzed for creatinine and specific gravity (SG). HC and norhydrocodone (NHC) appeared within 2 h followed by HM and DHC. Peak concentrations of HC and metabolites occurred at 3-9 h. Peak hydrolyzed concentrations were in the order: NHC > HC > HM > DHC. Only HM was excreted extensively as a conjugated metabolite. At a cutoff concentration of 50 ng/mL, detection times were ∼28 h for HC, 40 h for NHC, 26 h for HM and 16 h for DHC. Some specimens did not contain HC, but most contained NHC, thereby facilitating interpretation that HC was the administered drug. Creatinine and SG measures were highly correlated. Creatinine corrections of HC urinary data had variable effects of lowering or raising concentrations. These data suggest that drug-testing requirements for HC should include a hydrolysis step and a test for HM.

Non-smoker exposure to secondhand cannabis smoke. I. Urine screening and confirmation results

Increased cannabis potency has renewed concerns that secondhand exposure to cannabis smoke can produce positive drug tests. A systematic study was conducted of smoke exposure on drug-free participants. Six experienced cannabis users smoked cannabis cigarettes (5.3% THC in Session 1 and 11.3% THC in Sessions 2 and 3) in a sealed chamber. Six non-smokers were seated with smokers in an alternating manner. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Non-smoking participant specimens (collected 0-34 h) were analyzed with four immunoassays at different cutoff concentrations (20, 50, 75 and 100 ng/mL) and by GC-MS (LOQ = 0.75 ng/mL). No presumptive positives occurred for non-smokers at 100 and 75 ng/mL; a single positive occurred at 50 ng/mL; and multiple positives occurred at 20 ng/mL. Maximum THCCOOH concentrations by GC-MS for non-smokers ranged from 1.3 to 57.5 ng/mL. THCCOOH concentrations generally increased with THC potency, but room ventilation substantially reduced exposure levels. These results demonstrate that extreme cannabis smoke exposure can produce positive urine tests at commonly utilized cutoff concentrations. However, positive tests are likely to be rare, limited to the hours immediately post-exposure, and occur only under environmental circumstances where exposure is obvious.

Prescription Opioids. III. Disposition of Oxycodone in Oral Fluid and Blood Following Controlled Single-Dose Administration

Oxycodone (OC) is recommended to be included as an analyte tested in the proposed Substance Abuse and Mental Health Services Administration (SAMHSAs) Mandatory Guidelines for Federal Workplace Drug Testing Programs using Oral Fluid (OF) Specimens. This study demonstrates the time course of OC and metabolites, noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM), in near-simultaneous paired OF and whole blood (BL) specimens by liquid chromatography-tandem mass spectrometry (LC-MS-MS) (limit of detection = 1 ng/mL OF, 5 ng/mL BL). A single dose of OC 20 mg controlled-release was administered to 12 healthy subjects followed by specimen collections for 52 h. Analyte prevalence was as follows: OF, OC > NOC > OM; and BL, OC > NOC > NOM. OC and NOC were frequently detected within 15-30 min in OF and 30 min to 2 h in BL. NOM and OM appeared between 1.5-5 h post-dose. The mean OF-to-BL (OF:BL) ratios and correlations were 5.4 for OC (r = 0.719) and 1.0 for NOC (r = 0.651). The period of detection for OF exceeded BL by ∼2-fold at similar cutoff concentrations. At a 1 ng/mL cutoff for OF, the mean detection time was 34 h for OC and NOC. These data provide new information that should facilitate interpretation of OC test results.

Non-smoker exposure to secondhand cannabis smoke II: Effect of room ventilation on the physiological, subjective, and behavioral/cognitive effects

INTRODUCTION Cannabis is the most widely used illicit drug. Many individuals are incidentally exposed to secondhand cannabis smoke, but little is known about the effects of this exposure. This report examines the physiological, subjective, and behavioral/cognitive effects of secondhand cannabis exposure, and the influence of room ventilation on these effects. METHODS Non-cannabis-using individuals were exposed to secondhand cannabis smoke from six individuals smoking cannabis (11.3% THC) ad libitum in a specially constructed chamber for 1h. Chamber ventilation was experimentally manipulated so that participants were exposed under unventilated conditions or with ventilation at a rate of 11 air exchanges/h. Physiological, subjective and behavioral/cognitive measures of cannabis exposure assessed after exposure sessions were compared to baseline measures. RESULTS Exposure to secondhand cannabis smoke under unventilated conditions produced detectable cannabinoid levels in blood and urine, minor increases in heart rate, mild to moderate self-reported sedative drug effects, and impaired performance on the digit symbol substitution task (DSST). One urine specimen tested positive at using a 50 ng/ml cut-off and several specimens were positive at 20 ng/ml. Exposure under ventilated conditions resulted in much lower blood cannabinoid levels, and did not produce sedative drug effects, impairments in performance, or positive urine screen results. CONCLUSIONS Room ventilation has a pronounced effect on exposure to secondhand cannabis smoke. Under extreme, unventilated conditions, secondhand cannabis smoke exposure can produce detectable levels of THC in blood and urine, minor physiological and subjective drug effects, and minor impairment on a task requiring psychomotor ability and working memory.

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking.

Prescription Opioids. VI. Metabolism and Excretion of Hydromorphone in Urine Following Controlled Single-Dose Administration

Oxymorphone (OM), a prescription opioid and metabolite of oxycodone, was included in the recently published proposed revisions to the Mandatory Guidelines for Federal Workplace Drug Testing Programs. To facilitate toxicological interpretation, this study characterized the time course of OM and its metabolite, noroxymorphone (NOM), in hydrolyzed and non-hydrolyzed urine specimens. Twelve healthy subjects were administered a single 10 mg controlled-release OM dose, followed by a periodic collection of pooled urine specimens for 54 h following administration. Analysis for free and total OM and NOM was conducted by liquid chromatography tandem mass spectrometry (LC-MS-MS), at a 50 ng/mL limit of quantitation (LOQ). Following enzymatic hydrolysis, OM and NOM were detected in 89.9% and 13.5% specimens, respectively. Without hydrolysis, OM was detected in 8.1% specimens, and NOM was not detected. The mean ratio of hydrolyzed OM to NOM was 41.6. OM was frequently detected in the first pooled collection 0-2 h post-dose, appearing at a mean of 2.4 h. NOM appeared at a mean of 8.3 h. The period of detection at the 50 ng/mL threshold averaged 50.7 h for OM and 11.0 h for NOM. These data support that OM analysis conducted using a 50 ng/mL threshold should include hydrolysis or optimize sensitivity for conjugated OM.

Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults

Understanding the urine excretion profile for Δ9-tetrahydrocannabinol (THC) metabolites is important for accurate detection and interpretation of toxicological testing for cannabis use. Prior literature has primarily evaluated the urinary pharmacokinetics of the non-psychoactive THC metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) following smoked cannabis administration. The present study examined the urine THCCOOH excretion profile following oral cannabis administration in 18 healthy adults. Following ingestion of a cannabis-containing brownie with 10, 25 or 50 mg of THC (N = 6 per dose), urine specimens were collected on a closed residential research unit for 6 days, followed by three outpatient visits on Days 7-9. Average maximum concentrations (Cmax) of THCCOOH were 107, 335 and 713 ng/mL, and average times to maximum concentration (Tmax) were 8, 6 and 9 h for the 10, 25 and 50 mg THC doses, respectively. Detection windows to first positive and last positive varied as a function of dose; higher doses had shorter time to first positive and longer time to last positive. Considerable inter-subject variability was observed on study outcomes. Gas chromatography/mass spectrometry (GC/MS; 15 ng/mL cutoff) was used as the criterion to assess sensitivity, specificity and agreement for THCCOOH qualitative immunoassay tests using 20, 50 and 100 ng/mL cutoffs. The 50 ng/mL cutoff displayed good sensitivity (92.5%), specificity (92.4%) and overall agreement (92.4%), whereas the 20 ng/mL cutoff demonstrated poor specificity (58.4%), and the 100 ng/mL cutoff exhibited reduced sensitivity (70.9%). Ingestion of cannabis brownies containing the 10 and 25 mg THC doses yielded THCCOOH concentrations that differed in magnitude and time course from those previously reported for the smoked route of administration of comparable doses.