430 results on '"Cone, Edward"'
Search Results
2. Pharmacokinetics of Cannabis Brownies: A Controlled Examination of Δ9-Tetrahydrocannabinol and Metabolites in Blood and Oral Fluid of Healthy Adult Males and Females.
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Spindle, Tory R, Cone, Edward J, Herrmann, Evan S, Mitchell, John M, Flegel, Ronald, LoDico, Charles, Bigelow, George E, and Vandrey, Ryan
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SALIVA , *LIQUID chromatography-mass spectrometry , *MARIJUANA , *ENZYME-linked immunosorbent assay , *MOUTH - Abstract
Oral cannabis products (a.k.a. "edibles") have increased in popularity in recent years. Most prior controlled pharmacokinetic evaluations of cannabis have focused on smoked cannabis and included males who were frequent cannabis users. In this study, 17 healthy adults (8 females), with no cannabis use in at least the past 2 months, completed 4 double-blind outpatient sessions where they consumed cannabis brownies containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10, 25 or 50 mg. Whole blood and oral fluid specimens were collected at baseline and for 8 h post-brownie ingestion. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC–MS-MS) were used to measure THC and relevant metabolites. In whole blood, concentrations of THC and 11-hydroxy-THC (11-OH-THC) peaked 1.5–2 h after brownie consumption, decreased steadily thereafter, and typically returned to baseline within 8 h. Blood concentrations for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide were higher than THC and 11-OH-THC and these metabolites were often still detected 8 h post-brownie consumption. Women displayed higher peak concentrations for THC and all metabolites in whole blood compared to men, at least partially owing to their lower body weight/body mass index. Detection of THC in oral fluid was immediate and appeared to reflect the degree of cannabis deposition in the oral cavity, not levels of THC circulating in the blood. THC concentrations were substantially higher in oral fluid than in blood; the opposite trend was observed for THCCOOH. Agreement between ELISA and LC–MS-MS results was high (i.e. over 90%) for blood THCCOOH and oral fluid THC but comparatively low for oral fluid THCCOOH (i.e. 67%). Following oral consumption of cannabis, THC was detected in blood much later, and at far lower peak concentrations, compared to what has been observed with inhaled cannabis. These results are important given the widespread use of toxicological testing to detect recent use of cannabis and/or to identify cannabis intoxication. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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3. Urinary Pharmacokinetic Profile of Cannabinoids Following Administration of Vaporized and Oral Cannabidiol and Vaporized CBD-Dominant Cannabis.
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Spindle, Tory R, Cone, Edward J, Kuntz, David, Mitchell, John M, Bigelow, George E, Flegel, Ronald, and Vandrey, Ryan
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CANNABINOIDS , *CANNABIDIOL , *EMPLOYEE drug testing , *MEDICAL marijuana , *PHARMACOLOGY , *UNPLANNED pregnancy - Abstract
Cannabis products in which cannabidiol (CBD) is the primary chemical constituent (CBD-dominant) are increasingly popular and widely available. The impact of CBD exposure on urine drug testing has not been well studied. This study characterized the urinary pharmacokinetic profile of 100-mg oral and vaporized CBD, vaporized CBD-dominant cannabis (100-mg CBD; 3.7-mg ∆9-THC) and placebo in healthy adults (n = 6) using a within-subjects crossover design. Urine specimens were collected before and for 5 days after drug administration. Immunoassay (IA) screening (cutoffs of 20, 50 and 100 ng/mL) and LC–MS-MS confirmatory tests (cutoff of 15 ng/mL) for 11-nor-9-carboxy-∆9-tetrahydrocannabinol (∆9-THCCOOH) were performed; urine was also analyzed for CBD and other cannabinoids. Urinary concentrations of CBD were higher after oral (mean C max: 776 ng/mL) versus vaporized CBD (mean C max: 261 ng/mL). CBD concentrations peaked 5 h after oral CBD ingestion and within 1 h after inhalation of vaporized CBD. After pure CBD administration, only 1 out of 218 urine specimens screened positive for ∆9-THCCOOH (20-ng/mL IA cutoff) and no specimens exceeded the 15-ng/mL confirmatory cutoff. After inhalation of CBD-dominant cannabis vapor, nine samples screened positive at the 20-ng/mL IA cutoff, and two of those samples screened positive at the 50-ng/mL IA cutoff. Four samples that screened positive (two at 20 ng/mL and two at 50 ng/mL) confirmed positive with concentrations of ∆9-THCCOOH exceeding 15 ng/mL. These data indicate that acute dosing of pure CBD will not result in a positive urine drug test using current federal workplace drug testing guidelines (50-ng/mL IA cutoff with 15-ng/mL confirmatory cutoff). However, CBD products that also contain ∆9-THC may produce positive urine results for ∆9-THCCOOH. Accurate labeling and regulation of ∆9-THC content in CBD/hemp products are needed to prevent unexpected positive drug tests and unintended drug effects. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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4. Urinary Excretion Profile of 11-Nor-9-Carboxy-Δ9-Tetrahydrocannabinol (THCCOOH) Following Smoked and Vaporized Cannabis Administration in Infrequent Cannabis Users.
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Spindle, Tory R, Cone, Edward J, Schlienz, Nicolas J, Mitchell, John M, Bigelow, George E, Flegel, Ronald, Hayes, Eugene, and Vandrey, Ryan
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MARIJUANA , *EXCRETION , *URINALYSIS - Abstract
As cannabis has become more accessible, use of alternative methods for cannabis administration such as vaporizers has become more prevalent. Most prior controlled pharmacokinetic evaluations have examined smoked cannabis in frequent (often daily) cannabis users. This study characterized the urinary excretion profile of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH), the primary analytical outcome for detection of cannabis use, among infrequent cannabis users following controlled administration of both smoked and vaporized cannabis. Healthy adults (N = 17), with a mean of 398 (range 30–1,825) days since last cannabis use, smoked and vaporized cannabis containing 0, 10, and 25 mg of Δ9-tetrahydrocannabinol (THC) across six outpatient sessions. Urinary concentrations of THCCOOH were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity, and agreement between three immunoassays (IA) for THCCOOH (with cutoffs of 20, 50, and 100 ng/mL) and gas chromatography-mass spectrometry (GC/MS) results (confirmatory concentration of 15 ng/mL) were assessed. THCCOOH concentrations peaked 4–6 h after cannabis administration. Median maximum concentrations (Cmax) for THCCOOH were qualitatively higher after administration of vaporized cannabis compared to equal doses of smoked cannabis. Urine THCCOOH concentrations were substantially lower in this study relative to prior examinations of experienced cannabis users. The highest agreement between IA and GC/MS was observed at the 50 ng/mL IA cutoff while sensitivity and specificity were highest at the 20 and 100 ng/mL IA cutoffs, respectively. Using federal workplace drug-testing criteria (IA cutoff of 50 ng/mL and GC/MS concentration ≥15 ng/mL) urine specimens tested positive in 47% of vaporized sessions and 21% of smoked sessions with active THC doses (N = 68). Urinary concentrations of THCCOOH are dissimilar after administration of smoked and vaporized cannabis, with qualitatively higher concentrations observed after vaporization. Infrequent users of cannabis may excrete relatively low concentrations of THCCOOH following acute inhalation of smoked or vaporized cannabis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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5. The Postcard.
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Cone, Edward B.
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HISTORICAL fiction , *FICTION - Published
- 2023
6. Acute Pharmacokinetic Profile of Smoked and Vaporized Cannabis in Human Blood and Oral Fluid.
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Spindle, Tory R, Cone, Edward J, Schlienz, Nicolas J, Mitchell, John M, Bigelow, George E, Flegel, Ronald, Hayes, Eugene, and Vandrey, Ryan
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CANNABIS (Genus) , *VAPORIZATION , *PHARMACOKINETICS , *ENZYME-linked immunosorbent assay , *DRUG administration - Abstract
Currently, an unprecedented number of individuals can legally access cannabis. Vaporization is increasingly popular as a method to self-administer cannabis, partly due to perception of reduced harm compared with smoking. Few controlled laboratory studies of cannabis have used vaporization as a delivery method or evaluated the acute effects of cannabis among infrequent cannabis users. This study compared the concentrations of cannabinoids in whole blood and oral fluid after administration of smoked and vaporized cannabis in healthy adults who were infrequent users of cannabis. Seventeen healthy adults, with no past-month cannabis use, self-administered smoked or vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10 and 25 mg in six double-blind outpatient sessions. Whole blood and oral fluid specimens were obtained at baseline and for 8 h after cannabis administration. Cannabinoid concentrations were assessed with enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC–MS-MS) methods. Sensitivity, specificity and agreement between ELISA and LC–MS-MS results were assessed. Subjective, cognitive performance and cardiovascular effects were assessed. The highest concentrations of cannabinoids in both whole blood and oral fluid were typically observed at the first time point (+10 min) after drug administration. In blood, THC, 11-OH-THC, THCCOOH and THCCOOH-glucuronide concentrations were dose-dependent for both methods of administration, but higher following vaporization compared with smoking. THC was detected longer in oral fluid compared to blood and THCCOOH detection in oral fluid was rare and highly erratic. For whole blood, greater detection sensitivity for ELISA testing was observed in vaporized conditions. Conversely, for oral fluid, greater sensitivity was observed in smoked sessions. Blood and/or oral fluid cannabinoid concentrations were weakly to moderately correlated with pharmacodynamic outcomes. Cannabis pharmacokinetics vary by method of inhalation and biological matrix being tested. Vaporization appears to be a more efficient method of delivery compared with smoking. [ABSTRACT FROM AUTHOR]
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- 2019
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7. Pharmacokinetic Characterization of 11-nor-9- carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults.
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Schlienz, Nicolas J., Cone, Edward J., Herrmann, Evan S., Lembeck, Natalie A., Mitchell, John M., Bigelow, George E., Flegel, Ronald, LoDico, Charles P., Hayes, Eugene D., and Vandrey, Ryan
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TETRAHYDROCANNABINOL , *CANNABIS (Genus) , *PHARMACOKINETICS , *URINALYSIS , *IMMUNOASSAY , *GAS chromatography/Mass spectrometry (GC-MS) - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2018
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8. The ALERRT® instrument: a quantitative measure of the effort required to compromise prescription opioid abuse-deterrent tablets.
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Cone, Edward J., Buchhalter, August R., Lindhardt, Karsten, Elhauge, Torben, and Dayno, Jeffrey M.
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OPIOID abuse , *DRUG abuse , *INJECTION molding , *DRUG dosage , *SUBSTANCE abuse prevention , *ANALGESICS , *COMPARATIVE studies , *CONTROLLED release preparations , *RESEARCH methodology , *MEDICAL cooperation , *MORPHINE , *NARCOTICS , *RESEARCH , *DRUG tablets , *EVALUATION research - Abstract
Background: US FDA guidance recommends measuring the degree of effort needed to manipulate abuse-deterrent (AD) opioids. The ALERRT® instrument (PinneyAssociates; Bethesda, MD) uses visual analog scales to assess the labor, effort, and resources necessary to physically compromise AD product candidates in standardized settings.Objective: Use the ALERRT® instrument for testing morphine abuse-deterrent, extended-release, injection-molded tablets (ADER-IMT) 60 and 100 mg and the comparators immediate-release (IR) morphine sulfate 30 mg and extended-release (ER) morphine sulfate 60 mg.Methods: Four technicians tested the products using 10 household tools. The ALERRT instrument quantified effort (all tools) and time (3 preselected tools) required for manipulation.Results: Morphine-ADER-IMT 60 and 100 mg were difficult to manipulate, as demonstrated by high scores (mean range, 71.0-99.0 and 77.0-99.5, respectively). IR and ER morphine sulfate were easy to manipulate (low scores; mean range, 2.0-14.8 and 2.3-17.5, respectively). Statistically significant mean differences between morphine-ADER-IMT and comparators' ALERRT scores were observed. Manipulations of morphine-ADER-IMT 60 and 100 mg for 300 seconds failed to produce substantial powdering. Manipulations of IR morphine sulfate (mean range, 65.5-175.8 seconds) and ER morphine sulfate (49.3-163.0 seconds) produced substantial to complete powdering in 92% of tablets.Conclusions: Morphine-ADER-IMT was extremely difficult to manipulate versus non-AD formulations of morphine. The ALERRT system differentiated the degree of effort for manipulation of morphine-ADER-IMT and non-AD morphine formulations, indicating sensitivity of this instrument as part of Category 1 testing. By measuring the degree of effort required for manipulation, the ALERRT instrument provides an empirical assessment into the relative difficulty of manipulating opioid analgesics for abuse. [ABSTRACT FROM AUTHOR]- Published
- 2017
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9. Striving for Consensus on Approaches to Category 1 Testing of Abuse-Deterrent Formulations of Opioids: Discussions from the First Category 1 Focus Group Meeting.
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Cone, Edward J., Sokolowska, Marta, and Lindhardt, Karsten
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The article discusses the highlights of the discussions from the First Category 1 Focus Group Meeting regarding the testing of abuse-deterrent (AD) formulations of opioids. The 2015 Guidance for Industry: Abuse-Deterrent Opioids-Evaluation and Labeling" released by the U.S. Food and Drug Administration (FDA) is discussed. Category 1 determines AD characteristics through laboratory-based in vitro manipulation and extraction studies.
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- 2016
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10. Prescription Opioids. IV: Disposition of Hydrocodone in Oral Fluid and Blood Following Single-Dose Administration.
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Cone, Edward J., DePriest, Anne Z., Heltsley, Rebecca, Black, David L., Mitchell, John M., LoDico, Charles, and Flegel, Ron
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OPIOID analgesics , *OPIOIDS , *CARDIOVASCULAR system , *BODY fluids , *HUMAN body - Abstract
The Substance Abuse and Mental Health Services Administration (SAMHSA) is currently evaluating hydrocodone (HC) for inclusion in the Mandatory Guidelines for Federal Workplace Drug Testing Programs. This study evaluated the time course of HC, norhydrocodone (NHC), dihydrocodeine (DHC) and hydromorphone (HM) in paired oral fluid and whole blood specimens by liquid chromatography-- tandem mass spectrometry (limit of quantitation = 1 ng/mL of oral fluid, 5 ng/mL of blood) over a 52-h period. A single dose of HC bitartrate, 20 mg, was administered to 12 subjects. Analyte prevalence was as follows: oral fluid, HC > NHC > DHC; and blood, HC > NHC. HM was not detected in any specimen. HC was frequently detected within 15 min in oral fluid and 30 min in blood. Mean oral fluid to blood (OF : BL) ratios and correlations were 3.2 for HC (r = 0.73) and 0.7 for NHC (r = 0.42). The period of detection for oral fluid exceeded blood at all evaluated thresholds. At a 1-ng/mL threshold for oral fluid, mean detection time was 30 h for HC and 18 h for NHC and DHC. This description of HC and metabolite disposition in oral fluid following single-dose administration provides valuable interpretive guidance of HC test results. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.
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Cone, Edward J., Bigelow, George E., Herrmann, Evan S., Mitchell, John M., LoDico, Charles, Flegel, Ronald, and Vandrey, Ryan
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CANNABACEAE , *SMOKE , *BLOOD viscosity , *HUMAN anatomy , *CARDIOVASCULAR system - Abstract
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 drugfree nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ9-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. [ABSTRACT FROM AUTHOR]
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- 2015
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12. Non-smoker exposure to secondhand cannabis smoke II: Effect of room ventilation on the physiological, subjective, and behavioral/cognitive effects.
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Herrmann, Evan S., Cone, Edward J., Mitchell, John M., Bigelow, George E., LoDico, Charles, Flegel, Ron, and Vandrey, Ryan
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CANNABIS (Genus) , *VENTILATION , *COGNITIVE ability , *CIGARETTE smokers , *SELF-evaluation - Abstract
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 1 h. 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. [ABSTRACT FROM AUTHOR]
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- 2015
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13. Prescription Opioids. III. Disposition of Oxycodone in Oral Fluid and Blood Following Controlled Single-Dose Administration.
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Cone, Edward J., DePriest, Anne Z., Heltsley, Rebecca, Black, David L., Mitchell, John M., LoDico, Charles, and Flegel, Ron
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OPIOIDS , *OXYCODONE , *SALIVA , *LIQUID chromatography-mass spectrometry , *CLINICAL drug trials - Abstract
Oxycodone (OC) is recommended to be included as an analyte tested in the proposed Substance Abuse and Mental Health Services Administration (SAMHSA's) 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-releasewas 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. [ABSTRACT FROM AUTHOR]
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- 2015
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14. Non-Smoker Exposure to Secondhand Cannabis Smoke. I. Urine Screening and Confirmation Results.
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Cone, Edward J., Bigelow, George E., Herrmann, Evan S., Mitchell, John M., LoDico, Charles, Flegel, Ronald, and Vandrey, Ryan
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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 5 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. [ABSTRACT FROM AUTHOR]
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- 2015
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15. Ten Masterpieces of Music.
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Cone, Edward B.
- Published
- 2021
16. Prescription Opioids. II. Metabolism and Excretion Patterns of Hydrocodone in Urine Following Controlled Single-Dose Administration.
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Cone, Edward J., Heltsley, Rebecca, Black, David L., Mitchell, John M., LoDico, Charles P., and Flegel, Ronald R.
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DRUGS , *URINALYSIS , *DIHYDROCODEINE , *CLINICAL drug trials , *URINE , *CREATININE , *SPECIFIC gravity - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2013
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17. Reading Franz Liszt: Revealing the Poetry Behind the Piano Music.
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Cone, Edward B.
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COMPOSERS , *NONFICTION - Published
- 2022
18. Mozart: The Reign of Love.
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Cone, Edward B.
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NONFICTION - Published
- 2020
19. An iterative model for in vitro laboratory assessment of tamper deterrent formulations.
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Cone, Edward J., Giordano, Jennifer, and Weingarten, Brianne
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ITERATIVE methods (Mathematics) , *IN vitro studies , *MEDICAL prescriptions , *OPIOID abuse , *OXYCODONE , *EXCIPIENTS , *ANALGESICS , *NARCOTICS - Abstract
Background: In an effort to address the continuing problem of prescription opioid abuse, manufacturers are incorporating new technologies into formulations that are designed to deter product tampering and misuse. Standards for laboratory assessment of tamper deterrent properties of new formulations have not previously been developed. Methods: Experimental designs were developed for the in vitro laboratory assessment of the tamper deterrent properties of reformulated oxycodone. Given that an exhaustive study of all potential tampering methods was impractical; this model was developed to evaluate the product in an incremental fashion with iterative changes that were amenable to objective and replicable laboratory testing. Results: A description of the model is provided along with pertinent examples involving assessment of reformulated oxycodone with comparisons to the original formulation. Physical and chemical procedures were developed that relate to "real-world" scenarios that may be applied to opioid formulations. Test results were interpreted in relation to the relative ease or difficulty of the manipulation as compared to control materials and the amount and purity of active drug that could be accessed. Results from some of the tests were designed to be useful in predicting whether specific tampering methods would facilitate or deter drug administration by different routes of administration. Conclusions: This model, developed to assess the tamper deterrent properties of reformulated oxycodone, should have application in the assessment of other drug formulations designed to exhibit tamper deterrence properties. [ABSTRACT FROM AUTHOR]
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- 2013
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20. Prescription Opioids. I. Metabolism and Excretion Patterns of Oxycodone in Urine Following Controlled Single Dose Administration.
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Cone, Edward J., Heltsley, Rebecca, Black, David L., Mitchell, John M., LoDico, Charles P., and Flegel, Ronald R.
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OPIOID abuse , *DRUG prescribing , *DRUG metabolism , *EXCRETION , *OXYCODONE , *URINALYSIS , *DRUG dosage , *EPIDEMICS - Abstract
The ongoing epidemic of prescription opioid abuse in the United States has prompted interest in semi-synthetic opioids in the federal workplace drug testing program. This study characterized the metabolism and disposition of oxycodone (OC) in human urine. Twelve healthy adults were administered a single oral 20 mg dose of OC in a controlled clinical setting. Urine specimens were collected at timed intervals up to 52 h and analyzed by liquid chromatography–tandem mass spectrometry (limit of quantitation: 50 ng/mL) for OC, oxymorphone (OM), noroxycodone (NOC) and noroxymorphone (NOM) with and without enzymatic hydrolysis. OC and NOC appeared in urine within 2 h, followed by OM and NOM. Peak concentrations of OC and metabolites occurred between 3 and 19 h. Mean peak concentrations in hydrolyzed urine were in the following order: NOC > OC > OM > NOM. Only OM appeared to be excreted extensively as a conjugated metabolite. OC concentrations declined more quickly than NOC and OM. At a cutoff concentration of 50 ng/mL, detection times were approximately 30 h for OC and 40 h for NOC and OM. Some specimens did not contain OC, but most contained NOC, thereby facilitating interpretation that OC was the administered drug; however, five specimens contained only OM. These data provide information that should facilitate the selection of appropriate test parameters for OC in urine and assist in the interpretation of test results. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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21. Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration
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Polettini, Aldo, Cone, Edward J., Gorelick, David A., and Huestis, Marilyn A.
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METHAMPHETAMINE , *ORAL drug administration , *DRUG administration , *HAIR , *DRUG dosage , *CONTROLLED release drugs , *ISOPROPYL alcohol - Abstract
Abstract: Background: Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Material and methods: Seven volunteers with a history of stimulant use received 4×10mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC–MS–MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005ngmg−1). Results: MAMP T max occurred from 1 to 2 weeks after both doses, with C max ranging from 0.6 to 3.5ngmg−1 after the low and 1.2 to 5.3ngmg−1 after the high MAMP doses. AMP C max in hair was 0.1–0.3ngmg−1 and 0.2–0.5ngmg−1, respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2ngmg−1 cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15±0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r 2 =0.90, p =0.00) and AMP (r 2 =0.94, p =0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between C max and melanin. Conclusions: This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hair. [Copyright &y& Elsevier]
- Published
- 2012
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22. Oral fluid results compared to self reports of recent cocaine and heroin use by methadone maintenance patients
- Author
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Cone, Edward J.
- Subjects
- *
METHADONE abuse , *HEROIN abuse , *COCAINE , *SELF-evaluation , *DRUGS of abuse , *LIQUID chromatography , *TANDEM mass spectrometry , *SUBSTANCE abuse - Abstract
Abstract: Introduction: Although self reports of illicit drug use may not be reliable, this information is frequently collected and relied upon by national drug surveys and by counselors in drug treatment programs. The addition of oral fluid testing to these programs would provide objective information on recent drug use. Aim: The goal of this study was to compare oral fluid tests for cocaine, benzoylecgonine, 6-acetylmorphine, morphine, codeine and 6-acetylcodeine to self reports of recent cocaine and heroin use by patients in an outpatient methadone treatment program. Methods: Patients (n =400) provided an oral fluid specimen and completed a short questionnaire on illicit drug use over the last seven days. Oral fluid was collected with the Intercept® Oral Fluid Collection device. Oral fluid was analyzed by a validated assay using liquid chromatography coupled with tandem mass spectrometry. The presence of an analyte was confirmed if all identification criteria were met and its concentration (ng/mL) was ≥LOQ (cocaine, 0.4; benzoylecgonine, 0.4; morphine, 2; codeine, 2; 6-acetylmorphine, 0.4; and 6-acetylcodeine, 1). Results: Analyses of oral fluid specimens collected from the 400 methadone maintained patients revealed that a majority (95%) of subjects who admitted to recent cocaine use were confirmed positive, whereas slightly more than 50% were confirmed positive who admitted to heroin over the last seven days. For those patients who denied recent cocaine and heroin use, approximately 30% were positive for cocaine and 14% were positive for heroin. Conclusion: Oral fluid testing provides an objective means of verifying recent drug use and for assessment of patients in treatment for substance use disorders. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
23. Oral fluid results compared to self reports of recent cocaine and heroin use by methadone maintenance patients.
- Author
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Cone, Edward J
- Abstract
Abstract: Introduction: Although self reports of illicit drug use may not be reliable, this information is frequently collected and relied upon by national drug surveys and by counselors in drug treatment programs. The addition of oral fluid testing to these programs would provide objective information on recent drug use. Aim: The goal of this study was to compare oral fluid tests for cocaine, benzoylecgonine, 6-acetylmorphine, morphine, codeine and 6-acetylcodeine to self reports of recent cocaine and heroin use by patients in an outpatient methadone treatment program. Methods: Patients (n =400) provided an oral fluid specimen and completed a short questionnaire on illicit drug use over the last seven days. Oral fluid was collected with the Intercept® Oral Fluid Collection device. Oral fluid was analyzed by a validated assay using liquid chromatography coupled with tandem mass spectrometry. The presence of an analyte was confirmed if all identification criteria were met and its concentration (ng/mL) was ≥LOQ (cocaine, 0.4; benzoylecgonine, 0.4; morphine, 2; codeine, 2; 6-acetylmorphine, 0.4; and 6-acetylcodeine, 1). Results: Analyses of oral fluid specimens collected from the 400 methadone maintained patients revealed that a majority (95%) of subjects who admitted to recent cocaine use were confirmed positive, whereas slightly more than 50% were confirmed positive who admitted to heroin over the last seven days. For those patients who denied recent cocaine and heroin use, approximately 30% were positive for cocaine and 14% were positive for heroin. Conclusion: Oral fluid testing provides an objective means of verifying recent drug use and for assessment of patients in treatment for substance use disorders. [Copyright &y& Elsevier]
- Published
- 2012
24. Urine testing for norcodeine, norhydrocodone, and noroxycodone facilitates interpretation and reduces false negatives
- Author
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Cone, Edward J., Zichterman, Anne, Heltsley, Rebecca, Black, David L., Cawthon, Beverly, Robert, Tim, Moser, Frank, and Caplan, Yale H.
- Subjects
- *
URINALYSIS , *OXYCODONE , *DRUG use testing , *DRUGS of abuse , *BIOTRANSFORMATION (Metabolism) , *NARCOTICS , *LIQUID chromatography , *TANDEM mass spectrometry , *CODEINE - Abstract
Abstract: Urine drug testing of pain patients provides objective information to health specialists regarding patient compliance, diversion, and concurrent illicit drug use. Interpretation of urine test results for semi-synthetic opiates can be difficult because of complex biotransformations of parent drug to metabolites that are also available commercially and may be abused. Normetabolites such as norcodeine, norhydrocodone and noroxycodone are unique metabolites that are not available commercially. Consequently, detection of normetabolite in specimens not containing parent drug, provides conclusive evidence that the parent drug was consumed. The goal of this study was to evaluate the prevalence and patterns of the three normetabolites, norcodeine, norhydrocodone and noroxycodone, in urine specimens of pain patients treated with opiates. Urine specimens were hydrolyzed with β-glucuronidase and analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) assay for the presence of codeine, norcodeine, morphine, hydrocodone, norhydrocodone, hydromorphone, dihydrocodeine, oxycodone, noroxycodone, and oxymorphone. The limit of quantitation (LOQ) for these analytes was 50ng/mL. The study was approved by an Institutional Review Board. Of the total specimens (N =2654) tested, 71.4% (N =1895) were positive (≥LOQ) for one or more of the analytes. The prevalence (%) of positive results for codeine, hydrocodone and oxycodone was 1.2%, 26.1%, and 36.2%, respectively, and the prevalence of norcodeine, norhydrocodone and noroxycodone was 0.5%, 22.1%, and 31.3%, respectively. For specimens containing normetabolite, the prevalence of norcodeine, norhydrocodone and noroxycodone in the absence of parent drug was 8.6%, 7.8% and 9.4%, respectively. From one-third to two-thirds of these specimens also did not contain other metabolites that could have originated from the parent drug. Consequently, the authors conclude that inclusion of norcodeine, norhydrocodone and noroxycodone is useful in interpretation of opiate drug source and reduces potential false negatives that would occur without tests for these unique metabolites. [Copyright &y& Elsevier]
- Published
- 2010
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25. Normalization of Urinary Drug Concentrations with Specific Gravity and Creatinine.
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Cone, Edward J., Caplan, Yale H., Moser, Frank, Robert, Tim, Shelby, Melinda K., and Black, David L.
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- *
DRUGS , *URINATION , *CREATININE , *XENOBIOTICS , *HEROIN , *COCAINE , *DILUTION , *SPECIFIC gravity , *METABOLITES , *URINALYSIS - Abstract
The article presents a study which evaluates two drug normalization or correction processes based on specific gravity and creatinine in urinary drug concentrations. It notes that urination is one of the basic methods to remove xenobiotics in the body and various metabolites from the body. Urine concentrations can widely change and correlate reciprocally with urinary flow, and the excess of it could result in dilution. The study used three specimens from three distinct populations consist of pain patients, heroin users, and cocaine users. The result shows that specific gravity normalizations of drug concentrations developed twice in percent positives, small or changes in total percent positive rates, and a significant positive increase in cocaine users.
- Published
- 2009
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26. Rapid absorption of nicotine from new nicotine gum formulations
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Shiffman, Saul, Cone, Edward J., Buchhalter, August R., Henningfield, Jack E., Rohay, Jeffrey M., Gitchell, Joe G., Pinney, John M., and Chau, Tommy
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- *
ABSORPTION , *NICOTINE replacement therapy , *GUMS & resins , *PYRIDINE , *PHARMACOKINETICS , *SMOKING cessation - Abstract
Abstract: Rationale: A clinically limiting feature of currently-available nicotine gum is its slow rate of nicotine delivery and consequently slow onset of therapeutic effects. Previous research suggested that a nicotine hydrogen tartrate gum (NHTG1) that delivered nicotine more rapidly provided more effective craving relief. A subsequent gum formulation (NTHG2) was developed to further increase speed of delivery. Objective: Compare the plasma nicotine absorption and clinical tolerability of NHTG2 to NHTG1 and Nicorette® FreshMint™. Methods: A single-dose, randomized, crossover study evaluated the early kinetics of nicotine absorption and tolerability of 4 mg NHTG2 compared to NHTG1 and Nicorette. Results: NHTG2 gum reached higher C max (p =0.059 versus Nicorette; p =0.006 versus NHTG1) and delivered significantly more nicotine than Nicorette or NHTG1 within the first 10–30 min of chewing (AUCs0–10, 0–30) and overall (AUC0–180). NHT gums and Nicorette were well tolerated, with little difference in their AE profiles. Conclusions: Study results indicate that NHTG2 gum provided more rapid uptake of nicotine in blood without notable decreases in tolerability. To the extent that rate of delivery and onset of therapeutic effects are related, these gums would be expected to provide more rapid therapeutic effects. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
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27. Urine Drug Testing of Chronic Pain Patients: Licit and Illicit Drug Patterns.
- Author
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Cone, Edward J., Caplan, Yale J., Black, David L., Robert, Timothy, and Moser, Frank
- Subjects
- *
DRUG use testing , *CHRONIC pain , *CHRONICALLY ill , *DRUGS of abuse , *AMPHETAMINES , *BARBITURATES , *SUBSTANCE abuse , *URINALYSIS , *PATIENTS - Abstract
The article discusses the urine drug testing of chronic pain patients to determine licit and illicit drug patterns. A study is conducted to determine the drug disposition patterns in urine samples collected from a population of pain patients. The positive specimens were amphetamines, barbiturates, and benzodiazepines. The drug and metabolites were measured by gas chromatography and mass spectometry. The study also offers information on licit and illicit drug use, drug patterns and drug detection frequencies.
- Published
- 2008
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28. Evidence that Morphine is Metabolized to Hydromorphone But Not to Oxymorphone.
- Author
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Cone, Edward J., Caplan, Yale H., Moser, Frank, Robert, Tim, and Black, David
- Subjects
- *
MORPHINE , *URINALYSIS , *CLINICAL chemistry , *LIQUID chromatography , *MASS spectrometry , *CHROMATOGRAPHIC analysis , *NARCOTICS , *CLINICAL pathology - Abstract
The article focuses on determining an evidence that shows oxymorphone is a metabolic of morphine or hydromorphone. Urine specimens from pain patients were analyzed using liquid chromatography and mass spectrometry for morphone, hydromorphone and oxymorphone. Results from the urine specimens of patients treated high-dose morphine show hydromorphone while oxymorphone was not detected in any specimen. Thus, the authors concluded that oxymorphone is not a metabolite of either morphine or hydromorphone.
- Published
- 2008
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29. Prevalence and Disposition of Drugs of Abuse and Opioid Treatment Drugs in Oral Fluid.
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Cone, Edward J., Clarke, Joe, and Tsanaclis, Lolita
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- *
DRUGS of abuse , *CLINICAL chemistry , *PSYCHIATRIC drugs , *DRUG abuse , *DRUGS , *NARCOTICS , *STIMULANTS , *CLINICAL pathology , *BIOCHEMISTRY - Abstract
The article reports on several of the results of various laboratory tests which aimed to determine whether or not oral fluids could give evidence to drug abuse. According to the author, there have been studies conducted in order to determine the significance of oral fluids in the determination of chemical evidence related to drug abused; however, there is no evaluation made on oral fluids in relation to large population databases. The author cites the study which subjected oral fluids in a database taken from a commercial laboratory based in Great Britain. The study was able to derived positive results.
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- 2007
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30. Interpretation of Oral Fluid Tests for Drugs of Abuse.
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CONE, EDWARD J. and HUESTIS, MARILYN A.
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- *
ORAL medicine , *DRUG use testing , *DRUG abuse , *DRUG metabolism , *URINALYSIS , *CHEMICAL kinetics - Abstract
Oral fluid testing for drugs of abuse offers significant advantages over urine as a test matrix. Collection can be performed under direct observation with reduced risk of adulteration and substitution. Drugs generally appear in oral fluid by passive diffusion from blood, but also may be deposited in the oral cavity during oral, smoked, and intranasal administration. Drug metabolites also can be detected in oral fluid. Unlike urine testing, there may be a close correspondence between drug and metabolite concentrations in oral fluid and in blood. Interpretation of oral fluid results for drugs of abuse should be an iterative process whereby one considers the test results in the context of program requirements and a broad scientific knowledge of the many factors involved in determining test outcome. This review delineates many of the chemical and metabolic processes involved in the disposition of drugs and metabolites in oral fluid that are important to the appropriate interpretation of oral fluid tests. Chemical, metabolic, kinetic, and analytic parameters are summarized for selected drugs of abuse, and general guidelines are offered for understanding the significance of oral fluid tests. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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31. Methamphetamine Disposition in Oral Fluid, Plasma, and Urine.
- Author
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HUESTIS, MARILYN A. and CONE, EDWARD J.
- Subjects
- *
METHAMPHETAMINE , *SALIVA , *PLASMA chemistry , *URINE , *EXPERIMENTAL oral medicine , *MASS spectrometry - Abstract
This review of the disposition of methamphetamine in oral fluid, plasma, and urine is based on a comprehensive controlled dosing study involving five healthy, drug-free research volunteers who resided on a closed clinical ward for 12 weeks. Subjects were administered four low (10 mg) and high (20 mg) daily oral doses of methamphetamine in two separate sessions. Near-simultaneous collections of oral fluid and plasma were performed on the first day of each low- and high-dose session. Thereafter, oral fluid was provided on each day of dosing by different oral fluid collection methods. All urine specimens were collected on an ad libitum basis throughout the study. Specimens were analyzed by gas-chromatography mass spectrometry for methamphetamine and the metabolite, amphetamine, with a limit of quantification of 2.5 ng/mL for each analyte. Methamphetamine and metabolite concentrations in oral fluid appeared to follow a similar time course in oral fluid as in plasma and were dose-proportional, but oral fluid concentrations exceeded plasma concentrations. Urine drug concentrations were substantially higher than those in oral fluid. Some drug accumulation was noted with daily dosing, but generally did not markedly influence detection times or detection rates of oral fluid tests. Detection times and detection rates for oral fluid and urine were determined at cessation of 4 days of dosing. Generally, detection times and rates for urine were longer than those observed for oral fluid at conventional cutoff concentrations. When contemplating selection of oral fluid as a test matrix, the advantages of oral fluid collection should be weighed against its shorter time of detection compared to that of urine. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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- View/download PDF
32. A comparison between the Intercept Oral Fluid Collection Device® and urinalysis among Baltimore City probationers ☆ [1] The current study was funded by OraSure Technologies, Inc., in Bethlehem, Pennsylvania (www.orasure.com).
- Author
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Yacoubian, George S. and Cone, Edward J.
- Subjects
- *
CRIMINAL law , *JUSTICE , *NARCOTICS , *MARIJUANA - Abstract
Abstract: Few studies compared oral fluid (OF) analysis to laboratory urinalysis (UA) in real-world criminal justice environments, and no studies had collected survey data, from either specimen providers or specimen collectors, about the overall OF collection experience. In the most comprehensive toxicological comparison study conducted to date, urine and OF specimens were collected from a sample of 223 adult probationers in Baltimore City, Maryland, between March and May 2004. In addition, probationers and probation staff were surveyed about the OF collection experience. With confirmed UA as the reference standard, the Intercept Oral Specimen Collection Device® (Intercept) was 100 percent sensitive and 99 percent specific for benzodiazepines, 92 percent sensitive and 96 percent specific for cocaine, 77 percent sensitive and 96 percent specific for opiates, 39 percent sensitive and 98 percent specific for marijuana, and 75 percent sensitive and 91 percent specific for the detection of at least one drug. Seventy-two percent of the probationers and 88 percent of the probation staff rated the Intercept experience better than the collection of urine specimens. Implications for criminal justice policy and research are discussed. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
33. Evidence of Morphine Metabolism to Hydromorphone in Pain Patients Chronically Treated with Morphine.
- Author
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Cone, Edward J., Heit, Howard A., Caplan, Yale H., and Gourlay, Douglas
- Subjects
- *
MORPHINE , *METABOLITES , *CHRONIC pain , *TOXINS , *TOXICOLOGY - Abstract
The article describes an attempt to determine if credible clinical evidence exists for the metabolic conversion of morphine to hydromorphone by patients undergoing daily morphine treatment. Urine results of chronic pain patients who were being treated with morphine were examined. Data from the study highly suggest that hydromorphone can be produced as a minor metabolite of morphine in humans. It is recommended that interpretation of low urinary concentrations of hydromorphone in combination with high concentrations of morphine in morphine-treated pain patients should not be considered as conclusive evidence of hydromorphone misuse.
- Published
- 2006
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34. Oxycodone Involvement in Drug Abuse Deaths. II. Evidence for Toxic Multiple Drug-Drug Interactions.
- Author
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Cone, Edward J., Fant, Reginald V., Rohay, Jeffrey M., Caplan, Yale H., Ballina, Mayra, Reder, Robert F., and Haddox, J. David
- Subjects
- *
DEATH , *DRUG abuse , *OXYCODONE , *DRUG interactions , *DRUG toxicity - Abstract
Determines the involvement of oxycodone in drug abuse deaths. Adverse consequences of drug abuse; Evidence of enhanced toxicity associated with multiple drug-drug interactions; Assessment of blood levels by specific assay methodology.
- Published
- 2004
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35. Relationship of Δ9-Tetrahydrocannabinol Concentrations in Oral Fluid and Plasma after Controlled Administration of Smoked Cannabis.
- Author
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Huestis, Marilyn A. and Cone, Edward J.
- Subjects
- *
TETRAHYDROCANNABINOL , *CLINICAL drug trials , *DRUGS of abuse , *BLOOD plasma , *GAS chromatography , *MASS spectrometry - Abstract
Investigates the relationship of tetrahydrocannabinol (THC) concentrations in oral fluid and plasma and its importance in the interpretation of oral fluid test results. Source of THC; Analysis of plasma specimen by gas chromatography-mass spectrometry; Adoption of an oral fluid testing for drugs of abuse in a variety of settings.
- Published
- 2004
- Full Text
- View/download PDF
36. Oxycodone Involvement in Drug Abuse Deaths. II. Evidence for Toxic Multiple Drug-Drug Interactions.
- Author
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Cone, Edward J., Fant, Reginald V., Rohay, Jeffrey M., Caplan, Yale H., Ballina, Mayra, Reder, Robert F., and Haddox, J. David
- Subjects
- *
OXYCODONE , *ANALGESICS , *CODEINE derivatives , *NARCOTICS , *DRUG abuse , *TOXICOLOGY - Abstract
Investigates oxycodone (OXC) involvement in drug abuse deaths. Association of enhanced toxicity with multiple drug-drug interactions; Toxicity level between OXC in combination with other centrally acting drugs and OXC alone; Drug abuse patterns in multiple drug-induced cases.
- Published
- 2004
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- View/download PDF
37. Urine Testing for Cocaine Abuse: Metabolic and Excretion Patterns following Different Routes of Administration and Methods for Detection of False-Negative Results.
- Author
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Cone, Edward J., Sampson-Cone, Angela H., Darwin, William D., Huestis, Marilyn A., and Oyler, Jonathan M.
- Subjects
- *
COCAINE , *METABOLITES , *EXCRETION - Abstract
Examines urinary excretion and terminal elimination kinetics for cocaine and metabolites. Routes of administration; Elimination half-lives for cocaine and metabolites; Mean detection times.
- Published
- 2003
- Full Text
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38. Oxycodone Involvement in Drug Abuse Deaths: A DAWN-Based Classification Scheme Applied to an Oxycodone Postmortem Database Containing Over 1000 Cases.
- Author
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Cone, Edward J., Fant, Reginald V., Rohay, Jeffrey M., Caplan, Yale H., Ballina, Mayra, Reder, Robert F., Spyker, Daniel, and Haddox, J. David
- Subjects
- *
OXYCODONE , *DRUG tablets , *DRUG abuse , *DEATH , *SUBSTANCE abuse - Abstract
Evaluates the role of oxycodone and the specific drug product OxyContin tablets in the death of people with the help of oxycodone postmortem databases developed from solicited cases from Medical Examiner and Coroner offices in the U.S. Basis of oxycodone identification; Identification of tablets in gastrointestinal contents; Development of Drug Abuse Warning Network system for reporting drug abuse mortality data.
- Published
- 2003
- Full Text
- View/download PDF
39. The King at the Edge of the World.
- Author
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Cone, Edward
- Subjects
- *
HISTORICAL fiction , *FICTION - Abstract
A review of the book "The King at the Edge of the World: A Novel," by Arthur Phillips, is presented.
- Published
- 2020
40. The Colonel's Wife.
- Author
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Cone, Edward B.
- Subjects
- *
MILITARY personnel , *FASCISM , *FICTION - Published
- 2019
41. Prevalence of Cannabidiol, ∆9- and ∆8-Tetrahydrocannabinol and Metabolites in Workplace Drug Testing Urine Specimens.
- Author
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Vikingsson, Svante, Winecker, Ruth E, Cone, Edward J, Kuntz, David J, Dorsey, Brian, Jacques, Martin, Senter, Melanie, Flegel, Ronald R, and Hayes, Eugene D
- Subjects
- *
EMPLOYEE drug testing , *LIQUID chromatography-mass spectrometry , *CANNABIDIOL , *METABOLITES , *CANNABINOID receptors , *CANNABINOIDS - Abstract
Given the recent popularity of cannabidiol (CBD) use and the emergence of ∆8-tetrahydrocannabinol (∆8-THC), the prevalence and concentrations of these and other cannabinoids were investigated in 2,000 regulated and 4,000 non-regulated specimens from workplace drug testing. All specimens were screened using liquid chromatography coupled to mass spectrometry (LC–MS-MS) for the presence of 7-hydroxy-CBD (7-OH-CBD) and ∆9-tetrahydrocannabinol-9-carboxylic acid (∆9-THC-COOH), with a cutoff of 2 ng/mL. Specimens screening positive by LC–MS-MS were analyzed by immunoassay at 20, 50 and 100 ng/mL cutoffs and by an LC–MS-MS confirmation method for 11 cannabinoids and metabolites with a 1 ng/mL cutoff. Using a 1 ng/mL cutoff, 98 (4.9%) regulated and 331 (8.3%) non-regulated specimens were positive for ∆9-THC-COOH. Of these, 64% had concentrations below 15 ng/mL. Similarly, 59 (3.0%) regulated and 162 (4.2%) non-regulated specimens were positive for 7-OH-CBD (n = 210), CBD (n = 120) and/or 7-carboxy-cannabidiol (CBD-COOH, n = 120). The median concentrations of 7-OH-CBD, CBD and CBD-COOH in those 221 specimens were 6.3, 1.1 and 1.2 ng/mL, respectively. ∆8-Tetrahydrocannabinol-9-carboxylic acid (∆8-THC-COOH) was identified in 76 (1.3%) specimens. Parent ∆8-THC is a minor cannabinoid in marijuana, which appears to account for the typically low ∆8-THC-COOH concentrations (median 3.4 ng/mL) in most positive specimens. However, elevated concentrations suggested the use of ∆8-THC-containing products in some cases (range 1.0–415 ng/mL). Although 93% agreement was observed between confirmatory LC–MS-MS (15 ng/mL cutoff) and immunoassay (50 ng/mL cutoff), a false-negative specimen (66 ng/mL ∆9-THC-COOH) was identified. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
42. Pharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products.
- Author
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Bergeria, Cecilia L, Spindle, Tory R, Cone, Edward J, Sholler, Dennis, Goffi, Elia, Mitchell, John M, Winecker, Ruth E, Bigelow, George E, Flegel, Ronald, and Vandrey, Ryan
- Subjects
- *
CANNABIDIOL , *METABOLITES , *PHARMACOKINETICS , *VAPORIZATION , *INGESTION , *BIOAVAILABILITY - Abstract
There is limited data on the comparative pharmacokinetics of cannabidiol (CBD) across oral and vaporized formulations. This within-subject, double-blind, double-dummy, placebo-controlled laboratory study analyzed the pharmacokinetic profile of CBD, ∆9-tetrahydrocannabinol (∆9-THC) and related metabolites in blood and oral fluid (OF) after participants (n = 18) administered 100 mg of CBD in each of the following formulations: (1) oral CBD, (2) vaporized CBD and (3) vaporized CBD-dominant cannabis containing 10.5% CBD and 0.39% ∆9-THC (3.7 mg); all participants also completed a placebo condition. Oral CBD was administered in three formulations: (1) encapsulated CBD, (2) CBD suspended in pharmacy-grade syrup and (3) Epidiolex, allowing for pharmacokinetic comparisons across oral formulations (n = 6 per condition). An optional fifth experimental condition was completed for six participants in which they fasted from all food for 12 h prior to oral ingestion of 100 mg of CBD. Blood and OF samples were collected immediately before and for 57–58 h after each drug administration. Immunoassay screening and LC–MS-MS confirmatory tests were performed, the limit of quantitation was 0.5 ng/mL for ∆9-THC and 1 ng/mL for CBD. The mean C max and range of CBD blood concentrations for each product were as follows: vaporized CBD-dominant cannabis, 171.1 ng/mL, 40.0–665.0 ng/mL, vaporized CBD 104.6 ng/mL, 19.0–312.0 ng/mL and oral CBD, 13.7 ng/mL, 0.0–50.0 ng/mL. Of the three oral formulations, Epidiolex produced the greatest peak concentration of CBD (20.5 ng/mL, 8.0–37.0 ng/mL) relative to the capsule (17.8 ng/mL, 2.0–50.0 ng/mL) and syrup (2.8 ng/mL, 0–7.0 ng/mL). ∆9-THC was detected in the blood of 12/18 participants after vaporized CBD-dominant cannabis use, but neither ∆9-THC nor its metabolite THC-COOH were detected in the blood of any participants after vaporized or oral CBD-only administration. These data demonstrate that different oral and vaporized formulations produce substantial variability in the pharmacokinetics of CBD and that CBD alone is unlikely to convert to ∆9-THC or produce positive drug tests for ∆9-THC or its metabolite. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
43. Urinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Their Metabolites following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration.
- Author
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Sholler, Dennis J, Spindle, Tory R, Cone, Edward J, Goffi, Elia, Kuntz, David, Mitchell, John M, Winecker, Ruth E, Bigelow, George E, Flegel, Ronald R, and Vandrey, Ryan
- Subjects
- *
CANNABIS (Genus) , *CANNABIDIOL , *DRUG use testing , *BIOAVAILABILITY , *METABOLITES , *PHARMACOKINETICS , *CANNABINOIDS - Abstract
The market for products containing cannabidiol (CBD) is booming globally. However, the pharmacokinetics of CBD in different oral formulations and the impact of CBD use on urine drug testing outcomes for cannabis (e.g. 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH)) are understudied. This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18). A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast). Urine specimens were collected before and for 58 h after dosing on a residential research unit. Immunoassay (IA) screening (cutoffs: 20, 50 and 100 ng/mL) for Δ9-THCCOOH was performed, and quantitation of cannabinoids was completed via LC–MS-MS. Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax. Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-THC in any route or formulation in which pure CBD was administered. Following acute administration of vaporized CBD-dominant cannabis, 3 of 18 participants provided a total of six urine samples in which Δ9-THCCOOH concentrations ≥15 ng/mL. All six specimens screened positive at a 20 ng/mL IA cutoff, and two of six screened positive at a 50 ng/mL cutoff. These data show that absorption/elimination of CBD is impacted by drug formulation, route of administration and gastric contents. Although pure CBD is unlikely to impact drug testing, it is possible that hemp products containing low amounts of Δ9-THC may produce a cannabis-positive urine drug test. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
44. The Bridgetower Sonata.
- Author
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Cone, Edward
- Subjects
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HISTORICAL fiction , *FICTION - Published
- 2021
45. NEW WORLD ORDER.
- Author
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Cone, Edward
- Subjects
- *
COMPUTER software industry , *COMPUTER software , *APPLICATION service providers - Abstract
Focuses on the efforts of software manufacturers Microsoft Corp. and Oracle in building a software delivery and management model. Objective of the model; Importance of the model to the software products of Microsoft; Impact of the model on application service providers. INSET: TAKING THEIR BEST SHOT.
- Published
- 2001
46. Life in the e-Citi.
- Author
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Cone, Edward
- Subjects
- *
INTERNET - Abstract
Focuses on the revamp made to e-Citi company as an Internet Operating Group that reports to Citigroup executive, Deryck Maughan. Assets of e-Citi; Services offered by e-Citi; Responsibilities of Maughan; Business losses of e-Citi from 1997 to 1999; Significant tasks faced by e-Citi.
- Published
- 2000
47. e-loyalty.
- Author
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McGarvey, Joe and Cone, Edward
- Subjects
- *
EXECUTIVES , *CAREER changes - Abstract
Features several corporate executives with emphasis on their career changes. Harry Carr, chairman of Tellium; Navin Chaddha, chairman of Biztro; Jim Clark, chairman of myCFO.
- Published
- 2000
48. boys and their toys.
- Author
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Cone, Edward
- Subjects
- *
SPORTS team owners - Abstract
Features the owners of professional sports teams who made their fortunes in high technology business. Position of Paul Allen, owner of the Seattle Seahawks football team and the Portland Trail Blazers basketball team; Business sold by Marc Cuban, owner of the Dallas Mavericks basketball team, to Yahoo! that made him rich; Information on the business of Charles Wang and Sanjay Kumar, co-owners of the New York Islanders hockey team.
- Published
- 2000
49. Handel in London: A Genius and His Craft.
- Author
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Cone, Edward B.
- Subjects
- *
BAROQUE music , *COMPOSERS , *NONFICTION - Abstract
A review of the book "Handel in London: A Genius and His Craft," by Jane Glover, is presented.
- Published
- 2018
50. The Prisoner.
- Author
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Cone, Edward B.
- Subjects
- *
LOVE , *PARENTS , *FICTION - Published
- 2018
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