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Biomedical subjects

W D Darwin

Publications and source records attributed to W D Darwin.

At least 19 recordsLinked to original sources
PubMed2001

Urinary excretion profiles for total morphine, free morphine, and 6-acetylmorphine following smoked and intravenous heroin.

Heroin is one of the major target drugs in workplace drug-testing programs because of its history of abuse, liability, and continued negative social impact. This study was a comprehensive examination of pharmacokinetics, pharmacodynamics, detection times, opiate immunoassay performance, and urine excretion profiles following single doses of heroin administered to human subjects via smoking and intravenous routes. Studies of the first four components of this investigation were previously published. This article describes the urine excretion profiles. Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCI and four smoked 3.5-, 5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control samples were added to the study set to assess assay performance. Creatinine was also measured in each sample by a colorimetric technique. The parameters studied were not significantly dependent on route of administration. Excretion half-life mean +/- SD for Tmor was 3.11 +/- 0.30 h. Range (median) of peak urine concentrations, time to peak, time to last positive sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following lower doses (< or = 7 mg) were, respectively, 1392-9250 (3620) ng/mL, 1.2-6.2 (2.3) h, 7.4-31.9 (7.4) h, and 0-10.1 (4.3) h. Following higher doses (> 10 mg) they were 2065-29,030 (16,470) ng/mL, 2.3-9.3 (4.5) h, 10.7-53.5 (34.4) h, 2.3-22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor concentrations and time to last positive using a cutoff of 100 ng/mL for low and high doses were, respectively, 117-1160 (415) ng/mL, 1.2-10.1 (4.5) h and 150-2580 (1400) ng/mL, 2.3-29.1 (9.3) h. The range (median) of peak urine concentrations for 6-AM was 6.1-568 (124) ng/mL. In general, the first urine void had the peak 6-AM concentration and was the only specimen positive at a 10-ng/mL cutoff. As previously reported urine concentrations varied greatly between subjects and within subjects with time after dosing but were much more predictable when values were reported as amount of drug per unit of creatinine. The range (median) values for percent of heroin excreted into urine as Tmor was 12.8-88.5% (51.0).

Administration, Inhalation↗
PubMed2001

A comparison of Roche Kinetic Interaction of Microparticles in Solution (KIMS) assay for cannabinoids and GC-MS analysis for 11-nor-9-carboxy-delta9-tetrahydrocannabinol.

In this study, we investigated the effectiveness of the Roche Kinetic Interaction of Microparticles in Solution (KIMS) screening assay for cannabinoid metabolites. Urine specimens (N = 1689) were collected during elimination of cannabinoids from 25 subjects with a history of marijuana use. Specimens were analyzed concurrently for cannabinoid metabolites by a customized Department of Defense (DOD) cannabinoid KIMS kit (50-ng/mL cutoff) and for 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THC-COOH) by GC-MS (15-ng/mL cutoff). As compared to GC-MS results, the sensitivity, specificity, and efficiency of the KIMS assay were 69.7%, 99.8%, and 88.6%, respectively. Many of the false-negative results had GC-MS concentrations between 15 and 26 ng/mL (N = 151). The cannabinoid screening results for the DOD samples tested by the laboratory during the same 8-month period were also evaluated. The linear regression analyses of GC-MS results in the 15-50 ng/mL range and KIMS data resulted in regression coefficients of 0.689 for the research specimens and 0.546 for DOD specimens. The results suggest that the KIMS cannabinoid screening assay is deficient in detecting positives around the cutoff (15-25 ng/mL THC-COOH). This limitation of the KIMS cannabinoid screening method compromises the identification of true positive specimens, therefore reducing the effectiveness of the assay. The success of the DOD program is dependent on sensitive and specific screening assays; the high prevalence of false-negative cannabinoid results compromises the program's primary objective of drug deterrence.

Adult↗
PubMed2000

Detection times and analytical performance of commercial urine opiate immunoassays following heroin administration.

The Federal Workplace Drug Testing Program changed urine screening and confirmation cutoff concentrations for opiate testing from 300 to 2000 ng/mL in 1998. Morphine was the designated target compound. An additional heroin metabolite, 6-acetylmorphine (6-AM), was added to the testing procedure with a cutoff concentration > or = 10 ng/mL. Testing of 6-AM was required if morphine was positive to assist in medical review. A comparison of the new opiate cutoff concentrations was made with the older cutoff concentration at 300 ng/mL. Six commercial opiate immunoassays, four with a 300-ng/mL cutoff, ONLINE, EMIT, CEDIA and AxSym, and two with 2000-ng/mL cutoffs, ONLINE and EMIT, were selected to test 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCl and four smoked 3.5-, 5.2-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control specimens were added to the study set to assess linearity, cross-reactivity, and interference. Total morphine, free morphine, and 6-AM were measured in each sample by gas chromatography-mass spectrometry (GC-MS). Linearity, cross-reactivity, and interference results for each immunoassay are described. Detection times, sensitivity, specificity, and efficiency of each assay were determined using data from the specimens collected after heroin administration. Detection times for morphine using the 300-ng/mL cutoff assays was approximately 12 h for low dose and 24 to 48 h for higher doses of heroin. For the two 2000-ng/mL cutoff concentration assays detection time was about 12 h. This was also the detection time for 6-AM by GC-MS. ONLINE had the lowest sensitivity, 60-74%, highest specificity, 98.8-100%, and least interference from a selection of common over-the-counter drugs and opioids. Increasing the cutoff to 2000 ng/mL from 300 ng/mL increased efficiencies of the assays from 72.7 to 82.6% to over 97%.

Administration, Inhalation↗
PubMed1998

In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results.

Drug users can be highly motivated to obtain negative results on urine drug tests and may attempt to subvert the process by in vivo adulteration. The use of herbal products for "flushing" and "detoxification" is frequently advertised as an effective means of passing drug tests. Accordingly, a study was designed to determine the effects of ingestion of two herbal products, Naturally Klean Herbal Tea and Golden Seal root, and a diuretic medication, hydrochlorothiazide. The herbal tea was prepared in 1 gal of water as specified by the manufacturer. All other products were consumed with 1 gal of water. Two control conditions in which the subject consumed only water (1 gal; 12 oz) were included. The 1-gal liquid treatments were divided into 4-qt aliquots, and 1-qt was consumed each hour for 4 h. All treatments were begun approximately 22 h after smoking of a marijuana cigarette (3.58% THC) and 22 h after intranasal administration of cocaine hydrochloride. Following all treatments with excess fluid, creatinine and specific gravity dropped in 1.5-2.0 h to levels indicative of diluted specimens (<20 mg/dL creatinine, <1.003 specific gravity). Marijuana and cocaine metabolite concentrations by immunoassay (EMIT and TDx) also dropped rapidly, and the results frequently switched from positive to negative. By the time subjects had consumed 2 qt of any fluid, they were generally producing false-negative results. For example, ingestion of excess water produced dilute specimens (<20 mg/dL creatinine; <1.003 specific gravity) in an average time plus or minus the standard error of the mean of 1.47 +/- 0.17 h (N = 5) and 1.45 +/- 0.2 h (N = 5) following smoked marijuana and intranasal cocaine, respectively. In comparison, ingestion of Klean Tea produced dilute specimens in 1.36 +/- 0.07 h (N = 4) and 1.39 +/- 0.11 h (N = 4) following marijuana and cocaine administration. Recovery of urine test measures to pre-treatment levels occurred over a period of 8-10 h. Average detection times for marijuana metabolite appeared to be slightly shorter following ingestion of 1 gal of fluids compared with ingestion of 12 oz of water as a result of the time of testing being near the end of the cannabinoid metabolite excretion phase. Consequently, negative cannabinoid results induced by fluid ingestion rarely returned to positive after excess water was eliminated. In contrast, negative cocaine results reverted to positive quickly after the dilution effects disappeared. It was concluded that excess water ingestion can produce false-negative test results, but the claims of herbal products to be an aid in passing a urine test appear to be unfounded.

Adult↗
PubMed1998

Cocaine metabolism and urinary excretion after different routes of administration.

Cocaine abusers frequently self-administer cocaine by different routes of administration. A controlled-dosing study was performed to assess the effect of different routes of administration on the excretion profile of cocaine and metabolites in urine. Single bioequivalent doses of cocaine were administered by the intravenous, intranasal, and smoked routes to six human subjects. Urine specimens were collected for 3 days after drug administration and were analyzed for cocaine, metabolites, and anhydroecgonine methyl ester, the thermal degradation product of cocaine, by gas chromatography-mass spectrometry. Cocaine was rapidly absorbed, metabolized, and excreted in urine. Peak cocaine concentrations were generally present in the first specimen collected; thereafter, concentrations declined quickly and were usually below the limit of detection (approximately 1 ng/ml) within 24 hours. The metabolite benzoylecgonine was present in the highest concentration and represented approximately 39%, 30%, and 16%, of the administered dose by the intravenous, intranasal, and smoked routes, respectively. Combined amounts of ecgonine methyl ester and six minor metabolites (norcocaine, benzoylnorecgonine, m-hydroxycocaine, p-hydroxycocaine, m-hydroxybenzoylecgonine, and p-hydroxybenzoylecgonine) accounted for approximately 18%, 15%, and 8% of the administered dose by the intravenous, intranasal, and smoked routes, respectively. Anhydroecgonine methyl ester was present in trace amounts (0.02% dose) in specimens collected after smoked cocaine administration. Because many of these metabolites exhibit pharmacologic activity, their presence in urine may indicate that they play complex biologic roles in the overall activity of cocaine.

Administration, Inhalation↗
PubMed1997

Cocaine disposition in saliva following intravenous, intranasal, and smoked administration.

Saliva concentrations of cocaine, benzoylecgonine, ecgonine methyl ester, and anhydroecgonine methyl ester were measured by gas chromatography-mass spectrometry in six healthy male subjects following cocaine administration by the intravenous, intranasal, and smoked routes of administration. Cocaine appeared in saliva rapidly following all routes of administration. Saliva/plasma (S/P) ratios were generally greater than 1, and there was evidence of moderate to extreme contamination of saliva by cocaine immediately following intranasal and smoked routes of administration. Contamination of the oral cavity and saliva cleared rapidly. Saliva obtained 2 h after dosing appeared to be free of contamination and demonstrated S/P ratios comparable with intravenous administration. Benzoylecgonine and ecgonine methyl ester concentrations were consistently low and were only comparable with cocaine concentrations at times when cocaine concentrations had declined to below 100 ng/mL. Anhydroecgonine methyl ester was detectable in saliva following smoked drug administration, but it was quickly cleared. Terminal half-life estimates for cocaine administered by the intranasal and smoked routes were significantly shorter in saliva compared with those measured in plasma. Half-life estimates following intravenous administration tended to be lower for saliva than plasma, but the differences were not significant. The duration of pharmacologic effects was generally the same as or shorter than detection times of cocaine in plasma and saliva. Overall, the study demonstrated the usefulness of saliva as a test matrix for the detection and measurement of cocaine following administration by different routes of administration.

Administration, Inhalation↗
PubMed1996

Human pharmacokinetics of intravenous, sublingual, and buccal buprenorphine.

Buprenorphine is a potent opioid analgesic used in the treatment of moderate to severe pain. At higher doses, it has demonstrated potential for treating heroin dependence. This study was undertaken to investigate buprenorphine pharmacokinetics by different routes of administration at dosages approximating those used in opioid-dependence studies. Six healthy men who were nondependent but who had a history of heroin use were administered buprenorphine in a crossover design study by intravenous (1.2 mg), sublingual (4.0 mg), and buccal (4.0 mg) routes of administration. Plasma samples were collected up to 96 h and assayed for buprenorphine and norbuprenorphine by negative chemical ionization tandem mass spectrometry. Plasma concentrations of buprenorphine and norbuprenorphine were analyzed by nonlinear regression analysis with standard noncompartmental methods. Buprenorphine biovailability by the sublingual and buccal routes was estimated as 51.4% and 27.8%, respectively, although there was considerable interindividual variability by both routes of administration. The terminal elimination half-lives were longer for the sublingual and buccal routes than for the intravenous route. The extended elimination half-lives may be due to a shallow depot effect involving sequestration of buprenorphine in the oral mucosa. Norbuprenorphine mean peak plasma concentrations were less than 1 ng/mL and were highly variable among different routes of administration and individuals. The terminal elimination half-life of norbuprenorphine was longer than buprenorphine.

Administration, Buccal↗
PubMed1996

Forensic drug testing for opiates. VII. Urinary excretion profile of intranasal (snorted) heroin.

The urinary excretion profile of free and conjugated morphine and 6-acetylmorphine was determined by gas chromatography-mass spectrometry (GC-MS) and immunoassay for six healthy male subjects after intranasal administration of 6 and 12 mg of heroin HCI. Results were compared with heroin administration (6 mg) by the intramuscular route. Heroin metabolites were rapidly excreted with peak concentrations appearing in the first or second specimen collection after drug administration. Concentrations of total morphine and 6-acetylmorphine after intranasal heroin were similar to those after intramuscular administration, but free morphine concentrations after the lower intranasal dose were significantly lower than the same dose given intramuscularly. Detection times for total morphine by GC-MS and immunoassay (300-ng/mL cutoff concentration) were generally 24-36 h, but were reduced to less than 12 h at the higher cutoff concentration of 2000 ng/mL. 6-Acetylmorphine concentrations were highly variable and short-lived; detection times (10 ng/mL) were approximately 2-3 h for most subjects, but some failed to produce positive specimens. Of 14 specimens with 6-acetylmorphine concentrations of 10 ng/mL or more, ten were associated with total morphine concentrations greater than 2000 ng/mL, and four specimens had total morphine concentrations less than 2000 ng/mL. Overall, intranasal administration of heroin produced a similar profile of excretion of heroin metabolites to intramuscular administration.

Administration, Intranasal↗
PubMed1996

Cocaine disposition in meconium from newborns of cocaine-abusing mothers and urine of adult drug users.

The analysis of meconium for cocaine and metabolites has proved to be a reliable method for the detection of fetal cocaine exposure. Better sensitivity and a larger gestational window of detection have been demonstrated for meconium testing as compared with neonatal urine testing. Cocaine and cocaine metabolites, including benzoylecgonine, ecgonine methyl ester, cocaethylene, norcocaine, benzoylnorecgonine, and m-hydroxybenzoylecgonine, have been identified in meconium. The origin of these metabolites, whether maternal or fetal, has not been established. This study was conducted to compare the disposition of cocaine and metabolites in meconium from fetuses exposed to cocaine with that of urine from cocaine abusers. Meconium specimens were obtained from six neonates of mothers positive for cocaine use by urinalysis or self-reporting or both during pregnancy. Urine specimens were obtained from 17 adult female and 17 adult male cocaine users enrolled in a treatment program. Specimens were analyzed by gas chromatography-mass spectrometry for cocaine and 12 related analytes. The following analytes were identified and measured in meconium and urine: anhydroecgonine methyl ester; ecgonine methyl ester; ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; norcocaine; norcocaethylene; benzoylnorecgonine; m-and p-hydroxycocaine; and m-and p-hydroxybenzoylecgonine. In addition, both m-and p-hydroxybenzoylecgonine were found to exhibit approximately equal cross-reactivity with benzoylecgonine in the EMIT and TDx assays. The presence of p-hydroxybenzoylecgonine in meconium suggested that this newly identified metabolite, like m-hydroxybenzoylecgonine, might serve as a valuable marker of fetal cocaine exposure during pregnancy. The presence of cocaine and anhydroecgonine methyl ester in meconium was attributed to transfer across the placenta from the mother. However, the origin of the hydrolytic and oxidative metabolites of cocaine could not be established because they were also identified in urine specimens of adult female cocaine users and could have arisen in meconium from either fetal or maternal metabolism.

Adult↗
PubMed1995

Passive inhalation of cocaine.

Six healthy male volunteers were exposed to the vapor of 100 and 200 mg freebase cocaine heated to a temperature of 200 degrees C in an unventilated room (12,600-L volume) for a period of 1 h. No pharmacological effects were detected as a result of the exposure. Blood specimens collected immediately following exposure were negative for cocaine and metabolites. Urine specimens analyzed by gas chromatography-mass spectrometry contained peak concentrations of benzoylecgonine that ranged from 22 to 123 ng/mL. The peak excretion time for benzoylecgonine following passive exposure was approximately 5 h. The amount of cocaine inhaled by the subjects during passive exposure was estimated from room air measurements of cocaine to be approximately 0.25 mg. The total amount of cocaine (cocaine plus metabolites) excreted in urine by the six subjects ranged from 0.04 to 0.21 mg. For comparison, the six subjects also received an intravenous injection of 1 mg cocaine hydrochloride. Four of six subjects screened positive (300-ng/mL cutoff concentration) following the injection, indicating that the minimum amount of cocaine in these subjects necessary to produce positive results was approximately 1 mg. A second passive inhalation study was undertaken in which specimens were collected from research staff who assisted in a series of experimental studies with "crack" (freebase cocaine) smokers. The research staff remained in close vicinity while the crack smokers smoked three doses of freebase cocaine (12.5, 25, and 50 mg) over a period of 4 h. As a result, staff members were passively exposed to sidestream smoke from crack pipes and to breath exhalation from the crack smokers. Urine specimens from the staff members contained a maximum of 6 ng/mL benzoylecgonine. Only traces (less than 1 ng/mL) of cocaine were detected in any specimen. Overall, these studies demonstrated that individuals exposed to cocaine smoke under naturalistic or artificial conditions absorbed small amounts of cocaine that were insufficient to produce positive urine specimens at standard Department of Health and Human Services cutoffs. However, passive exposure conditions that would result in absorption of cocaine in amounts exceeding 1 mg could result in the production of cocaine-positive urine specimens.

Administration, Inhalation↗
PubMed1994

Simultaneous assay of cocaine, heroin and metabolites in hair, plasma, saliva and urine by gas chromatography-mass spectrometry.

As part of an ongoing research program on the development of drug detection methodology, we developed an assay for the simultaneous measurement of cocaine, heroin and metabolites in plasma, saliva, urine and hair by solid-phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS). The analytes that could be measured by this assay were the following: anhydroecgonine methyl ester; ecgonine methyl ester;. ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; cocaethylene; norcocaethylene; benzoylnorecgonine; codeine; morphine; norcodeine; 6-acetylmorphine; normorphine; and heroin. Liquid specimens were diluted, filtered and then extracted by SPE. Additional handling steps were necessary for the analysis of hair samples. An initial wash procedure was utilized to remove surface contaminants. Washed hair samples were extracted with methanol overnight at 40 degrees C. Both wash and extract fractions were collected, evaporated and purified by SPE. All extracts were evaporated, derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) and analyzed by GC-MS. The limit of detection (LOD) for cocaine, heroin and metabolites in biological specimens was approximately 1 ng/ml with the exception of norcodeine, normorphine and benzoylnorecgonine (LOD = 5 ng/ml). The LOD for cocaine, heroin and metabolites in hair was approximately 0.1 ng/mg of hair with the exception of norcodeine (LOD = 0.3 ng/mg) and normorphine and benzoylnorecgonine (LOD = 0.5 ng/mg). Coefficients of variation ranged from 3 to 26.5% in the hair assay. This assay has been successfully utilized in research on the disposition of cocaine, heroin and metabolites in hair, plasma, saliva and urine and in treatment studies.

Cocaine↗
PubMed1994

Sweat testing for heroin, cocaine, and metabolites.

Although a variety of drugs have been detected in sweat, little information is available on the characteristics of drug excretion in sweat under controlled-dosing conditions. A series of clinical studies were designed to determine the identity, concentration, time course, dose dependency, and variability of drug and metabolite excretion in sweat following administration of single doses of cocaine and heroin to human subjects. Sweat was collected by means of a sweat patch that could be worn for a period of several days to several weeks at a time, resulting in accumulation of drug in the patch. Sweat patches were removed at specified times and frozen until analyzed by gas chromatography--mass spectrometry. Cocaine and heroin were the major analytes excreted in sweat following their administration. Smaller amounts of cocaine metabolites were also detected following cocaine administration. 6-Acetylmorphine appeared rapidly after heroin administration and continued to increase while heroin content decreased, suggesting that heroin was undergoing hydrolysis in the sweat patch. Cocaine appeared in sweat within 1-2 hours and peaked within 24 hours in an apparent dose-dependent manner. Analysis of duplicate adjacent patches from individual subjects who had been administered cocaine provided similar quantitative results, suggesting that intrasubject variability was relatively low, whereas intersubject variability was high. These observations regarding the excretion of cocaine and heroin analytes in sweat have important forensic implications to other fields such as hair analysis. Sweat excretion could be an important mechanism by which drugs enter hair. These data also suggest that the sweat patch could serve as a useful monitoring device in surveillance of individuals in treatment and probation programs.

Administration, Inhalation↗
PubMed1994

Simultaneous measurement of cocaine, cocaethylene, their metabolites, and "crack" pyrolysis products by gas chromatography-mass spectrometry.

We developed a sensitive and specific assay for the simultaneous measurement of cocaine, cocaethylene, six of their metabolites, and anhydroecgonine methyl ester, a pyrolysis product, in biological fluids. The assay involves solid-phase extraction columns containing a copolymeric bonded phase for isolation of cocaine analytes, derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide and 10 g/L trimethylchlorosilane, and measurement with gas chromatography-mass spectrometry operating in the selected-ion monitoring mode. Detector responses for analytes were linear over a concentration range of 3.1-1000 micrograms/L. The limits of detection were approximately 1 microgram/L for cocaine, ecgonine methyl ester, and benzoylecgonine and 3-6 micrograms/L for the remaining analytes. Hydrolysis of cocaine and artifact formation of anhydroecogonine methyl ester during extraction and assay was < 1%. Cocaine and its derivatives appear in different proportions in plasma, saliva, and urine according to the biological fluid and time of measurement. Each biological fluid provides unique information on the disposition of cocaine in human subjects.

Administration, Intranasal↗
PubMed1993

The occurrence of cocaine, heroin and metabolites in hair of drug abusers.

The analysis of hair for drugs of abuse reveals information regarding past drug exposure. We developed methods for washing, extraction and analysis of hair samples for cocaine, heroin and metabolites. Twenty paired head- and arm-hair samples, collected from known heroin/cocaine abusers, were analyzed with a new comprehensive GC/MS assay for cocaine, heroin and metabolites. Cocaine and 6-acetylmorphine (6-AM) were the major analytes present in both head- and arm-hair samples. Cocaine was detected in all head- and 17 arm-hair samples. The concentration of cocaine found was 4-760 ng/10 mg in head hair and 0-1090 ng/10 mg in arm hair. Less benzoylecgonine was present in a concentration range of 0-158 ng/10 mg of head hair and 0-125 ng/10 mg of arm hair. Heroin was found in only 2 head-hair samples, whereas 6-AM was present in 14 head and 6 arm-hair samples. The concentration of 6-AM was 0-8 ng/10 mg in head hair and 0-31 ng/10 mg in arm hair. Morphine was present in 3 head-hair samples in a range of 2-9 ng/10 mg and was not detected in arm-hair samples. When results were compared by groups (head hair versus arm hair, Caucasoid versus Africoid), only two significant differences were found. Cocaine concentrations in both head and arm hair were significantly (P < 0.05) higher in the Africoid group than in the Caucasoid group. The reasons for these differences were not readily apparent, but could have been due to differences in the level of cocaine use or to ethnic differences in the deposition of drug in hair.

Adult↗
PubMed1993

Validity testing of the EZ-SCREEN cannabinoid test.

Recently, a number of "quick tests" became available for use in on-site drug testing. These tests offer advantages in simplicity, ease of performance, and rapid access to test results. However, there is a paucity of data on the validity of these tests for the detection of drugs of abuse. This report describes a validity study of the EZ-SCREEN cannabinoid test for the detection of cannabinoids in urine. Three healthy, male volunteers with a history of marijuana use participated in the study. Each subject smoked 1, 2, or 4 marijuana cigarettes (2.6% THC) on each test day. Urine samples were collected and incorporated into a specimen set consisting of 178 clinical urine 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 EZ-SCREEN test and by GC/MS for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Results were interpreted independently by three readers. Concordance analysis was performed by comparison of results of the EZ-SCREEN test with GC/MS. The EZ-SCREEN test was highly sensitive and produced positive results at a standard THCCOOH concentration of 5 ng/mL. While showing high sensitivity to THCCOOH, the assay demonstrated low cross-reactivity with delta 9-tetrahydrocannabinol (THC) and other cannabinoids. No false-positive results were recorded with 50 drug-free urine samples, but one reader recorded eight undecided results. Overall agreement between the three readers for the EZ-Screen results was approximately 80%. Delayed readings and photocopy readings tended to be less accurate than readings obtained at 3 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Pharmacokinetics and pharmacodynamics of intranasal "snorted" heroin.

The purity of illicit heroin in the United States has increased steadily over the last several years, while prices have fallen. Associated with this trend, there has been a recent shift among heroin addicts from intravenous injection to intranasal use ("snorting"). Because of the lack of information on this route of administration, we evaluated the pharmacokinetic and pharmacodynamic properties of intranasal heroin. Results were compared to the effects of heroin by the intramuscular route. Six healthy, male volunteers were administered single doses of intranasal heroin hydrochloride (6 and 12 mg), intramuscular heroin hydrochloride (6 mg), and placebo. Blood levels of heroin, 6-acetylmorphine, and morphine were measured by gas chromatography/mass spectrometry. Simultaneous physiological, behavioral, and performance measures were obtained. Peak blood levels of heroin were attained within 5 min of heroin administration by the intranasal route, similar to those observed for intramuscular administration. Generally, the pharmacokinetic profile of intranasal heroin was equivalent to that for the intramuscular route. Physiological, behavioral, and performance effects following intranasal administration were similar to the effects following intramuscular administration. The relative potency of intranasal heroin was estimated to be approximately one-half that of intramuscular administration. The efficacy of the intranasal route, combined with decreased heroin cost, reduced fear of infection, and the lack of requirements for additional drug paraphernalia, could make this an attractive route of drug administration to naive or infrequent drug users.

Administration, Inhalation↗
PubMed1993

Cocaine and metabolite excretion in saliva under stimulated and nonstimulated conditions.

The accessibility of saliva for rapid, noninvasive sampling makes it an attractive biological fluid for detecting drug use. However, little is known about salivary excretion patterns of the major cocaine metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME). Additionally, there is a general lack of information on the effects of salivary collection conditions on cocaine excretion in saliva. This study documents the profile of cocaine and metabolites in human saliva under stimulated and nonstimulated saliva flow conditions. Saliva samples were obtained periodically from six healthy volunteers who were administered three, equally spaced, single intravenous doses of 25 mg of cocaine during a 6-h test session. On different days, whole saliva was obtained either under nonstimulated or stimulated (sour candy) conditions. The samples were analyzed for cocaine and metabolites by GC/MS. Cocaine, BE, and EME were detected and quantitated in the saliva of all subjects. Cocaine was the predominant analyte identified in all samples. Nonstimulated saliva contained substantially more drug than stimulated samples. The ratio of the area under the curve (AUC) of cocaine in nonstimulated saliva to that of stimulated saliva was variable and ranged from 3.0 to 9.5. The AUC ratios of BE and EME were similar to those observed for cocaine. The lowering of cocaine concentration in saliva in the stimulated flow condition was likely due to an increase in saliva pH associated with increased saliva flow rate; it is known that an increase in saliva pH retards cocaine partitioning into this biological fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗