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Biomedical subjects

E J Cone

Publications and source records attributed to E J Cone.

179 records · Page 10Linked to original sources
PubMedDate not supplied

Interference by nonsteroidal anti-inflammatory drugs in EMIT and TDx assays for drugs of abuse.

Fourteen nonsteroidal anti-inflammatory drugs were evaluated for interference in EMIT and TDx assays for drugs of abuse. Only tolmetin demonstrated significant interferences in the EMIT assay. Urine samples that contained high concentrations of tolmetin (1800 mg/L) had characteristic high molar absorptivity at the wavelength used in EMIT assays (340 nm). Consequently, EMIT analysis of samples resulted in instrument error alarms on a Hitachi 704 instrument and depressed milliabsorbance values (delta A) relative to calibrators. Similar results were obtained with urine samples collected from an arthritic patient after the administration of 200 and 400 mg of tolmetin. When tolmetin samples were mixed with drugs of abuse, depressed delta A values were noted in all assays. Samples containing opiates and cannabinoids tested negative, and instrument error alarms were produced with samples that contained amphetamines. A gas chromatographic-mass spectrometric (GC-MS) assay for benzoylecgonine in the presence of tolmetin was successful, and no interferences were noted. Similar interferences by tolmetin were not observed in TDx assays, probably because of the different wavelength (525 nm) used in this assay. However, a potential for false-positive results in the TDx benzodiazepine assay was noted for urine samples containing high concentrations of fenoprofen, flurbiprofen, indomethacin, ketoprofen, and tolmetin. Generally, it was concluded that the presence of tolmetin in urine samples could lead to the production of unacceptable results by the EMIT assay for drugs of abuse. However, TDx and GC-MS assays were useful alternatives for the analysis of urine samples suspected of containing tolmetin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Forensic drug testing for opiates. VI. Urine testing for hydromorphone, hydrocodone, oxymorphone, and oxycodone with commercial opiate immunoassays and gas chromatography-mass spectrometry.

Opiate testing for morphine and codeine is performed routinely in forensic urine drug-testing laboratories in an effort to identify illicit opiate abusers. In addition to heroin, the 6-keto-opioids, including hydromorphone, hydrocodone, oxymorphone, and oxycodone, have high abuse liability and are self-administered by opiate abusers, but only limited information is available on detection of these compounds by current immunoassay and gas chromatographic-mass spectrometric (GC-MS) methods. In this study, single doses of hydromorphone, hydrocodone, oxymorphone, and oxycodone were administered to human subjects, and urine samples were collected before and periodically after dosing. Opiate levels were determined in a quantitative mode with four commercial immunoassays, TDx opiates (TDx), Abuscreen radioimmunoassay (ABUS), Coat-A-Count morphine in urine (CAC), and EMIT d.a.u. opiate assay (EMIT), and by GC-MS. GC-MS assay results indicated that hydromorphone, hydrocodone, oxymorphone, and oxycodone administration resulted in rapid excretion of parent drug and O-demethylated metabolites in urine. Peak concentrations occurred within 8 h after drug administration and declined below 300 ng/mL within 24-48 h. Immunoassay testing indicated that hydromorphone, hydrocodone, and oxycodone, but not oxymorphone, were detectable in urine by TDx and EMIT (300-ng/mL cutoff) for 6-24 h. ABUS detected only hydrocodone, and CAC failed to detect any of the four 6-keto-opioid analgesics. Generally, immunoassays for opiates in urine displayed substantially lower sensitivities for 6-keto-opioids compared with GC-MS. Consequently, urine samples containing low to moderate concentrations of hydromorphone, hydrocodone, oxymorphone, and oxycodone will likely go undetected when tested by conventional immunoassays.

Enzyme Multiplied Immunoassay Technique↗
PubMedDate not supplied

Validity testing of the accuPINCH THC test.

Self-contained drug-testing kits are currently being marketed for a variety of drugs of abuse. These tests are designed to provide rapid access to test results without the need for laboratory facilities. This report describes a validity study of the accuPINCH THC test, a self-contained test for cannabinoids in urine. Three healthy male volunteers with a history of marijuana use participated in the clinical study. Each subject smoked one, two, or four marijuana cigarettes (2.6% THC) on each test day. Urine samples were collected and incorporated into a specimen set consisting of 178 clinical samples, 72 urine samples containing known amounts of drug, and 50 drug-free urine samples. The specimen set was randomized and analyzed under blind conditions by the accuPINCH test and by gas chromatography-mass spectrometry (GC-MS) for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). AccuPINCH results were interpreted independently by three readers as positive at either two calibration points (positive A < 100 ng/mL THCCOOH; positive B > or = 100 ng/mL THCCOOH) or negative. Concordance analysis was performed by comparison of the accuPINCH results with GC-MS. In addition, the effects of changes in sample turbidity, temperature, and assay reading time on test outcome were assessed. For the clinical samples, positive B results were associated exclusively with THCCOOH concentrations greater than or equal to 15 ng/mL, whereas positive A and negative results were obtained at all concentrations. All drug-free urine samples were interpreted as either negative or positive A. The test demonstrated relatively low cross-reactivity with THC and other cannabinoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Cocaine contamination of United States paper currency.

The exchange of illicit cocaine for money by drug dealers is an everyday occurrence in cities in the United States. There is ample opportunity during the exchange, storage, and use of cocaine for paper currency to become contaminated. Because currency is exchanged frequently, it is likely that contaminated currency would be found in common use. We examined ten single dollar bills from several cities in the United States for the presence of cocaine. Individual bills were extracted with methanol (10 mL). Cocaine was purified from the methanol extract by solid-phase extraction (SPE). The SPE extract was analyzed by gas chromatography-mass spectrometry (GC-MS). Standard curves were constructed with new, uncirculated currency. Cocaine was identified qualitatively by full scan and quantitated by selected ion monitoring. Cocaine was present in 79% of the currency samples analyzed in amounts above 0.1 micrograms and in 54% of the currency in amounts above 1.0 micrograms. Contamination was widespread and was found in currency from all sites examined. Cocaine amounts were highly variable and ranged from nanogram to milligram amounts. The highest amount of cocaine detected on a single one-dollar bill was 1327 micrograms. These results indicated that cocaine contamination of currency is widespread throughout the United States and is likely to be primarily a result of cross-contamination from other contaminated currency and from contaminated money-counting machines.

Cocaine↗
PubMedDate not supplied

Plasma concentrations of heroin and morphine-related metabolites after intranasal and intramuscular administration.

The disposition of heroin and its metabolites was investigated in four healthy male volunteers following intranasal administration of 6 and 12 mg heroin hydrochloride. In addition, two doses of 6 mg heroin hydrochloride were injected intramuscularly for comparison of pharmacokinetic parameters. Serum samples were analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction-gas chromatography-mass spectrometry. The concentration of morphine glucuronides was determined by high-performance liquid chromatography based on the native fluorescence of the conjugates. Major findings were rapidly rising and declining terminal phases for heroin and 6-acetylmorphine and slowly declining phases of morphine and metabolites after both routes of administration. The area under the curve values of morphine-3-glucuronide depended on dose but not on route of administration. The apparent terminal half-lives of morphine-3-glucuronide ranged from 2.2 to 5.2 h for intranasally administered heroin and were 3.0 and 1.7 h for the intramuscularly applied drug. A mean morphine-3-glucuronide-heroin area-under-curve ratio of 93 for the intranasal route as compared with 38 for the intramuscular route demonstrated that circulating amounts of heroin were about half the size after intranasal administration of the same dose.

Administration, Intranasal↗
PubMedDate not supplied

Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum.

This study examined the disposition of cocaine, codeine, and metabolites in stratum corneum, sebum, and plasma collected from five African-American males after administrations of cocaine and codeine during a 10-week inpatient clinical study. The subjects were experienced, healthy drug users with a recent history of cocaine and heroin abuse. The first drug administration was delayed by three weeks to allow for the elimination of previously administered drugs from the body. Subjects received three 75 mg cocaine hydrochloride/70 kg doses by the subcutaneous route and three 60 mg codeine sulfate/70 kg doses by the oral route on alternating days beginning in week 4. The same dosing sequence was repeated in week 8 with doubled (x 2) doses. Pharmacological measures (heart rate, pupil diameter, subject "High" and "Liking") were obtained simultaneously with blood. Stratum corneum was collected by scraping regions of the back once each week. Sebum was collected periodically from the forehead by applying Sebutape patches for 1-2-h intervals. Plasma, stratum corneum, and sebum were analyzed for cocaine, codeine, and metabolites by gas chromatography-mass spectrometry. Peak plasma cocaine concentrations occurred within the 30 min following dosing and followed peak pharmacological effects. Peak plasma codeine concentrations occurred within 1-2 h of dosing and before peak pharmacological effects. Cocaine and codeine were the primary analytes in sebum and stratum corneum. After dosing, these drugs appeared in sebum within 1-2 h and were detected for 1-2 days. Peak-drug concentrations in stratum corneum occurred one day after completion of dosing; elimination of the drugs continued over the next 1-2 weeks after dosing. Overall, no definitive relationship was observed between drug concentrations in sebum and stratum corneum compared with dose. Interpretation of drug distribution and elimination in sebum and stratum corneum was complicated by possible contamination of specimens with drugs from sweat. The mechanism(s) for deposition of cocaine and codeine in sebum and stratum corneum appeared to be complex and could involve the transfer of drugs between different body fluids (i.e., sebum and sweat) and other matrices (i.e., skin and hair).

Administration, Oral↗
PubMedDate not supplied

Occurrence of cocaine in urine of substance-abuse treatment patients.

As part of ongoing research efforts to improve methods of monitoring drug use in treatment patients, the presence of cocaine in urine specimens was evaluated as a possible marker for recent illicit cocaine use. A total of 2327 urine specimens collected during a 17-week clinical trial of a cocaine-abuse treatment study were tested. Cocaine was measured by gas chromatography-mass spectrometry, and benzoylecgonine (BZE) equivalents were determined by fluorescence polarization immunoassay (FPIA). More than one-third of the specimens were positive (> 25 ng/mL) for cocaine (36.8%), and nearly two-thirds were positive (> 300 ng/mL) for cocaine metabolite by FPIA (62.7%). Median concentrations of cocaine and BZE equivalents were 235 and 14,900 ng/mL, respectively, and maximum concentrations were 112,025 and 1,101,190 ng/mL in cocaine- and BZE-positive specimens, respectively. There were 52 specimens that contained cocaine in equal or higher concentrations than BZE equivalents. No significant differences in cocaine or BZE concentrations between Caucasian and African-American or between male and female patients were found. Cocaine was present less frequently and at lower concentrations than BZE but more frequently than expected based on an average half-life of approximately 1 h, which suggests that cocaine may exhibit a longer terminal half-life and/or that accumulation of cocaine can occur in chronic, heavy users.

Adolescent↗
PubMedDate not supplied

Detection of marijuana use by oral fluid and urine analysis following single-dose administration of smoked and oral marijuana.

We compared oral fluid testing to urine testing in subjects who were administered single doses of marijuana by smoked and oral routes. Oral fluid specimens were collected with the Intercept DOA Oral Specimen Collection Device, screened for THC with the Cannabinoids Intercept MICRO-PLATE Enzyme Immunoassay (EIA) utilizing a 1.0-ng/mL cutoff concentration, and confirmed for THC by gas chromatography-tandem mass spectrometry (GC-MS-MS) with a 0.5-ng/mL cutoff concentration. Urine specimens were screened for 11-nor-carboxy-delta9-tetrahydrocannabinol (THCCOOH) by immunoassay utilizing a 50-ng/mL cutoff concentration and confirmed for THCCOOH by GC-MS with a 15-ng/mL cutoff concentration. Oral fluid specimens tested positive following smoked marijuana (N = 10) consecutively for average periods (+/-SEM; range) of 15 (+/-2; 1-24) and 13 h (+/-3; 1-24) by EIA and GC-MS-MS, respectively. The average THC detection times of the last oral fluid positive specimen following smoked marijuana by EIA and GC-MS-MS were 31 (+/-9; 1-72) and 34 h (+/-11; 1-72), respectively. In comparison to oral fluid, urine specimens generally tested negative for THCCOOH immediately after marijuana use. The average times to detection of the first urine specimen positive for THCCOOH by EIA and GC-MS were 6 (+/-2; 1-16) and 4 h (+/-1; 2-8), respectively. Urine specimens tested positive consecutively for average periods of 26 (+/-9; 2-72) and 33 h (+/-10; 4-72) for EIA and GC-MS, respectively. The average THCCOOH detection times of the last specimen by EIA and GC-MS were 42 (+/-10; 2-72) and 58 h (+/-6; 16-72), respectively. Considering the noninvasive nature of oral fluid collection and improved detection of recent marijuana use compared to urine testing, it was concluded that oral fluid testing for THC offers specific advantages over other means of marijuana testing when used in safety-sensitive testing programs.

Administration, Oral↗
PubMedDate not supplied

Morphine pharmacokinetics during anesthesia and surgery in patients with burns.

The plasma clearance, plasma half-life, and apparent volume of distribution of morphine during anesthesia and surgery were determined in seven patients with burns and compared with seven age-matched control subjects. The burn group had a significantly lower clearance, longer terminal half-life, and smaller volume of distribution than the control group. The clearance was 12 +/- 2 ml/min/kg, the half-life was 123 +/- 24 minutes, and the volume of distribution was 2.2 +/- 0.4 L/kg for the subjects with burns compared with 25 +/- 3 ml/min/kg, 89 +/- 18 minutes, and 3.2 +/- 0.8 L/kg for the control subjects (p less than 0.001, less than 0.02, and less than 0.02, respectively). These data contrast with the theory that patients with burns have a tolerance to narcotics and suggest the need for further study of the pharmacologic effects of burn injury and surgery.

Adult↗
PubMedDate not supplied

Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog.

The metabolism of hydrocodone was studied in man, rat, guinea pig, rabbit, and dog. Routes of metabolism included O-demethylation, N-dealkylation, and 6-keto-reduction to the corresponding 6-alpha- and 6-beta-hydroxy metabolites, where each metabolic pathway produces an active metabolite. Mean total recovery of drug and metabolites as percentage of administered dose ranged from a low of 10.6% for the rabbit to a high of 46.8% for the guinea pig; man was intermediate at 25.7%. For man, approximately 70% of the total drug recovered was excreted in the first 24 hr, and the remainder by 72 hr. Considerable species differences were observed in the patterns of metabolism of hydrocodone. Also, stereoselectivity of 6-keto reduction to the beta-form was observed for all species in the reduction of hydrocodone and hydromorphone with the exception of the reduction of hydrocodone by man.

Adult↗
PubMedDate not supplied

Analytical controls in drug metabolic studies. II. Artifact formation during chloroform extraction of drugs and metabolites with amine substituents.

Chemical artifacts are readily produced during chloroform extractions of drugs and metabolites with amine substituents by the reaction of chloroform contaminants, phosgene and ethyl chloroformate, to form carbamoyl chlorides and carbamates. Chloroform obtained from three different suppliers was examined with regard to the effects of preservatives and exposure to air on the quantity and nature of these contaminants. Extractions with chloroform obtained from a supplier's sealed bottle and containing ethanol preservative produced the least amount of artifact. With previously opened bottles (prior exposure to air, open), the amount of artifact formation rose substantially. Chloroform without preservative or with a nonpolar hydrocarbon preservative likewise produced large amounts of artifacts during extraction. Attempts to purify chloroform showed that distillation was ineffective for the removal of phosgene or ethyl chloroformate, whereas their effective removal was accomplished by solvent elution through a column of activated alumina or upon standing over calcium hydroxide powder. Possible artifact formation must be considered in drug-metabolism studies and appropriate controls included for the detection and elimination of chemical artifacts.

Amines↗
PubMedDate not supplied

The metabolism and excretion of buprenorphine in humans.

Buprenorphine, a powerful mixed agonist-antagonist analgesic which shows promise of providing maintenance pharmacotherapy for heroin addicts, is metabolized in male human subjects to norbuprenorphine and to conjugated buprenorphine and norbuprenorphine. Following subcutaneous, sublingual, and oral buprenorphine administration to a single subject, total metabolite excretion in urine was 2, 13.4, and 12.1%, respectively. No free parent drug was detected in urine. The amount of norbuprenorphine metabolite excreted in urine generally exceeded that of conjugated buprenorphine. In contrast, free and conjugated buprenorphine equaled or greatly exceeded total norbuprenorphine content in fecal samples following oral or sublingual administration. The greatest amount of drug and metabolite eliminated in feces occurred at 4 to 6 days following buprenorphine administration at times when there was very little urinary excretion of conjugated buprenorphine. This latter evidence indicates an enterohepatic circulation of buprenorphine in humans.

Adult↗
PubMedDate not supplied

Oxymorphone metabolism and urinary excretion in human, rat, guinea pig, rabbit, and dog.

Oxymorphone was extensively metabolized by human, rat, dog, and guinea pig and to a lesser extent by rabbit. The most abundant metabolite in urine for all species was conjugated oxymorphone (12.7-81.7% administered dose) followed by 6 beta- and 6 alpha-carbinols produced by 6-keto reduction of oxymorphone. 6 beta-Oxymorphol (0.2-3.1%) was found in the urine of all species, whereas 6 alpha-oxymorphol (0.1-2.8%) was found only in human, rabbit, and guinea pig. Small amounts of free oxymorphone (less than or equal to 10%) were excreted by all species except rabbit, which excreted 31.7%. Overall recoveries of oxymorphone and metabolites from urine ranged from 15-96%, of which greater than 80% was excreted in the first 24 hr by all species except dog. Only 35% was excreted by dog during the first day. Stereoselectivity of 6-keto- reduction was observed for all species with the 6 beta-carbinol metabolite being most abundant in the urine of all but guinea pig. Considerable individual variability occurred in the excretion of free and conjugated oxymorphone by six human subjects following oral dosing. Species trends in the metabolism of 6-keto-opioids are discussed.

Adult↗