Benzoylecgonine Concentrations Research Articles

Concentrations of cocaine and its major metabolite benzoylecgonine in blood samples from apprehended drivers in Sweden

Cocaine and its major metabolite benzoylecgonine (BZE) were determined in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID) over a 5-year period (2000–2004). Venous blood or urine if available, was subjected to a broad toxicological screening analysis for cannabis, cocaine metabolite, amphetamines, opiates and the major benzodiazepines. Verification and quantitative analysis of cocaine and BZE in blood was done by gas chromatography-mass spectrometry (GC–MS) at limits of quantitation (LOQ) of 0.02 mg/L for both substances. Over the study period 26,567 blood samples were analyzed and cocaine and/or BZE were verified in 795 cases (3%). The motorists using cocaine were predominantly men (>96%) with an average age of 28.3 ± 7.1 years (±standard deviation, S.D.). The concentration of cocaine was below LOQ in 574 cases although BZE was determined at mean, median and highest concentrations of 0.19 mg/L, 0.12 mg/L and 1.3 mg/L, respectively. In 221 cases, cocaine and BZE were together in the blood samples at mean and (median) concentrations of 0.076 mg/L (0.05 mg/L) and 0.859 mg/L (0.70 mg/L), respectively. The concentrations of BZE were always higher than the parent drug; mean BZE/cocaine ratio 14.2 (median 10.9) range 1–55. Cocaine and BZE were the only psychoactive substances reported in N = 61 cases at mean (median) and highest concentrations of 0.095 (0.07) and 0.5 mg/L for cocaine and 1.01 (0.70) and 3.1 mg/L for BZE. Typical signs of drug influence noted by the arresting police officers included bloodshot and glossy eyes, agitation, difficulty in sitting still and incoherent speech.

Detection and quantification of low levels of benzoylecgonine in equine urine

Cocaine (COC) is a highly addictive plant alkaloid expressing strong psychostimulatory effect. It has no medical use in equine veterinary practice. The contamination of the environment with cocaine such as its presence on the US paper currency has been reported few times. There are anecdotal reports of low benzoylecgonine (BE) concentrations (usually much less than 100 ng/mL) being found in urine of race horses. In order to protect horsemen against harsh penalties associated with the presence of trace amounts of BE in horse urine as a result of environmental contamination, in February 2005 the Illinois Racing Board issued new medication rules that established the threshold level of 150 ng/mL for BE in equine urine. The penalties associated with this rule provide for increasing fines ($250, $500, $1000) with successive positive reports against a trainer for levels of BE below 150 ng/mL. A total of 19,315 urine samples were collected over the 2-year period of time from winning horses (both harness and thoroughbred) at race tracks in Illinois for routine drug screening (ELISA). The presence of BE was confirmed by GC/MS in 28 urine samples (0.14%). The concentration range for BE in harness horses (21 detections) was <5–91 ng/mL, and for thoroughbred (seven detections) was 7–52 ng/mL. To date, the laboratory has not reported concentrations of BE that exceed the established threshold concentration of 150 ng/mL.

Cocaine-related deaths: An enigma still under investigation

In recent years there has been an increase interest in cocaine-related death reflecting the rising trend in cocaine use in Europe. Nevertheless is still now very difficult to attribute a death to cocaine. We can affirm that cocaine can be responsible for the cause of death only when there is a reasonably complete understanding of the circumstances or facts surrounding the death. Isolated blood cocaine levels are not enough to assess lethality, should be always considered and evaluated in relation to concentrations of cocaine and benzoylecgonine concentrations in body tissue compartments, especially in brain and blood. We have reanalyzed all of our cocaine-related case from 1990 to 2005, applying the methodology used by Spielher and Reed over 30 years ago. Our aim was to try to validate this model and verify its applicability and effectiveness after 20 years.

Distribution of drugs of abuse within specific regions of the human brain

Since concentration of drugs of abuse found in the brain better reflect drug concentration at their site of action, brain specimens are useful in the determination of the role of drugs of abuse in the cause of death. In order to allow for the routine use of brain specimens in this field, a comprehensive database with reliable reference values is needed and should include both post-mortem data for cases where drugs have been taken in therapeutic doses as well as for cases of overdose. In this study, a semi-automated extraction procedure, in combination with gas chromatography/mass spectrometry (GC–MS) using stable isotope internal standards was applied to yield reproducible, quantitative results which could be used to investigate the distribution patterns of drugs of abuse within specific regions of the brain, by analyzing several segments of both medulla oblongata and cerebellum. A homogenous distribution of unconjugated morphine, dihydrocodeine, and benzoylecgonine within the investigated segments of medulla oblongata or cerebellum could be found. However, when these two brain regions from the same case were compared to each other, significantly higher concentrations of unconjugated morphine, dihydrocodeine, and benzoylecgonine were found in the cerebellum than in the medulla oblongata.

Psychosocial functioning and cocaine use during treatment: Strength of relationship depends on type of urine-testing method

Although improvement in psychosocial functioning is a common goal in substance-abuse treatment, the primary outcome measure in most cocaine trials is urinalysis-verified cocaine use. However, the relationship between cocaine use and psychosocial outcomes is not well documented. To investigate this relationship and identify the optimal urine-screen method, we retrospectively analyzed data from two 25-week randomized controlled trials of abstinence reinforcement (AR) in 368 cocaine/heroin users maintained on methadone. Cocaine use was measured thrice weekly by qualitative urinalysis, benzoylecgonine concentration (BE), and an estimate of New Uses of cocaine by application of an algorithm to BE. Social adjustment (SAS-SR), current diagnosis of cocaine dependence (DSM-IV criteria), and depression symptoms (Beck Depression Inventory) were determined at study exit. Cocaine use was significantly lower in AR groups than in controls. Across groups, in-treatment cocaine use was significantly associated with worse social adjustment, current cocaine dependence, and depression at exit. Significant differences were detected more frequently with New Uses than qualitative urinalysis or BE. Nevertheless, the amount of variance accounted for by the urine screens was typically <15%. Cocaine use during treatment, especially when measured with New Uses criteria, can predict psychosocial functioning, but cannot substitute for direct measures of psychosocial functioning.

Pharmacokinetic profile of cocaine following intravenous administration in the female rabbit

Prenatal cocaine exposure in a rabbit intravenous model has revealed selective disruption of brain development and pharmacological responsiveness. We therefore examined the pharmacokinetic properties of cocaine in this model. Dutch-belted rabbits were surgically implanted with a catheter in the carotid artery, allowed to recover, and then injected intravenously with a cocaine bolus. Cocaine and benzoylecgonine concentrations were measured in arterial blood plasma and analyzed by nonlinear regression and noncompartmental analyses. Peak cocaine concentration occurred by 30s, was transient, and distribution was rapid. The profile of cocaine in the rabbit is similar to that observed in humans using cocaine at recreational doses.

Coca tea consumption causes positive urine cocaine assay

Coca tea, derived from the same plant that is used to synthesize cocaine, is commonly consumed in South America and easily obtained in the United States. To determine whether consumption of coca tea would result in a positive urine toxicology screen for cocaine metabolites. Five healthy adult volunteers consumed coca tea and underwent serial quantitative urine testing for cocaine metabolites by fluorescence polarization immunoassay. The cutoff for a positive assay was chosen at 300 ng/ml, the National Institute on Drug Abuse standard. Each participant's urine cocaine assay was positive (level exceeding 300 ng/ml) by 2 h after ingestion. Three out of five participants' samples remained positive at 36 h. Mean urine benzoylecgonine concentrations in all postconsumption samples was 1777 ng/ml (95% confidence interval: 1060-2495). Coca tea ingestion resulted in a positive urine assay for cocaine metabolite. Healthcare professionals should consider a history of coca tea ingestion when interpreting urine toxicology results.

Imaging Brain Mu-Opioid Receptors in Abstinent Cocaine Users: Time Course and Relation to Cocaine Craving

Cocaine treatment upregulates brain mu-opioid receptors (mOR) in animals. Human data regarding this phenomenon are limited. We previously used positron emission tomography (PET) with [11C]-carfentanil to show increased mOR binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of abstinence. Regional brain mOR binding potential (BP) was measured with [11C]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on a research ward and in 16 healthy control subjects. Mu-opioid receptor BP was increased in the frontal, anterior cingulate, and lateral temporal cortex after 1 day of abstinence. Mu-opioid receptor BP remained elevated in the first two regions after 1 week and in the anterior cingulate and anterior frontal cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was positively correlated with self-reported cocaine craving. Mu-opioid receptor BP was significantly correlated with percentage of days with cocaine use and amount of cocaine used per day of use during the 2 weeks before admission and with urine benzoylecgonine concentration at the first PET scan. These results suggest that chronic cocaine use influences endogenous opioid systems in the human brain and might explain mechanisms of cocaine craving and reinforcement.

Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence

The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence. A multi-arm, modified blinded, placebo-controlled design was used. The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU). Participants met criteria for cocaine dependence during a 2-week screening period. Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study. Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period. None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated. This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.

Concentration profiles of cocaine, pyrolytic methyl ecgonidine and thirteen metabolites in human blood and urine: determination by gas chromatography-mass spectrometry

When cocaine is smoked, a pyrolytic product, methyl ecgonidine (anhydroecgonine methyl ester), is also consumed with the cocaine. The amount of methyl ecgonidine formed depends on the pyrolytic conditions and composition of the illicit cocaine. This procedure describes detection of cocaine and 10 metabolites--cocaethylene, nor-cocaine, nor-cocaethylene, methyl ecgonine, ethyl ecgonine, benzoylecgonine, nor-benzoylecgonine, m-hydroxybenzoylecgonine, p-hydroxybenzoylecgonine and ecgonine--in blood and urine. In addition, the detection of pyrolytic methyl ecgonidine and three metabolites--ecgonidine (anhydroecgonine), ethyl ecgonidine (anhydroecgonine ethyl ester) and nor-ecgonidine (nor-anhydroecgonine)--are included. The newly described metabolites, ethyl ecgonidine and nor-ecgonidine, were synthesized and characterized by gas chromatography-mass spectrometry (GC-MS). All 15 compounds were extracted from 3 mL of blood or urine by solid-phase extraction and identified by a GC-MS method. The overall recoveries were 49% for methyl ecgonine, 35% for ethyl ecgonine, 29% for ecgonine and more than 83% for all other drugs. The limits of detection were between 0.5 and 4.0 ng/mL except for ecgonine, which was 16 ng/mL. Linearity for each analyte was established and in all cases correlation coefficients were 0.9985-1.0000. The procedure was applied to examine the concentration profiles of analytes of interest in post-mortem (PM) blood and urine, and in urine collected from living individuals (LV). These specimens previously were shown to be positive for the cocaine metabolite, benzoylecgonine. Ecgonidine, the major metabolite of methyl ecgonidine, was present in 77% of PM and 88% of the LV specimens, indicating smoking as the major route of cocaine administration. The new pyrolytic metabolites, ethyl ecgonidine and nor-ecgonidine, were present in smaller amounts. The urine concentrations of nor-ecgonidine were 0-163 ng/mL in LV and 0-75 ng/mL in PM specimens. Ethyl ecgonidine was found only in PM urine at concentrations 0-39 ng/mL. Ethanol-related cocaine metabolites, ethyl ecgonine or cocaethylene, were present in 69% of PM and 53% of cocaine-positive LV specimens, implying alcohol consumption with cocaine use. The four major metabolites of cocaine--benzoylecgonine, ecgonine, nor-benzoylecgonine and methyl ecgonine--constituted approximately 88 and 97% of all metabolites in PM and LV specimens, respectively. The concentrations of nor-cocaine and nor-cocaethylene were consistently the lowest of all cocaine metabolites. At benzoylecgonine concentrations below 100 ng/mL, ecgonine was present at the highest concentrations. In 20 urine specimens, benzoylecgonine and ecgonine median concentrations (range) were 54 (0-47) and 418 ng/mL (95-684), respectively. Therefore, detection of ecgonine is advantageous when benzoylecgonine concentrations are below 100 ng/mL.

Cocaine-related fatalities in New South Wales, Australia 1993–2002

Aim: To ascertain the demographic characteristics, circumstances of death, toxicological results, and major autopsy findings of cocaine-related fatalities. Design: Inspection of the coronial records of all cocaine-related deaths that occurred in New South Wales, Australia between 1 January 1993 and 31 December 2002. Setting: New South Wales, Australia. Findings: 146 cases were identified. Cocaine was implicated in the direct cause of death in 86% of cases, an antecedent cause in 8% and a significant condition contributing to death in 7%. The mean age of decedents was 34.1years, and 84% were male. Half were employed, and 26% were in professional employment. The predominant route of administration was injection (86%), however nasal (8%), oral (3%), smoking (1%), and anal (1%) administration were all recorded. The most common location of death was a private home (53%). No intervention occurred prior to death in 82% of cases. The median blood benzoylecgonine concentration was 0.40 mg/L (range 0.00–20.00 mg/L). Cases had a mean of 3.5 drugs, with morphine (79%) the most common co-occurring drug. In 5% of cases cocaine was the sole drug detected. Cardiac pathology was noted in 57% of cases, most commonly coronary artery atherosclerosis (39%) and cardiac hypertrophy (14%). In 15% of cases moderate to severe arterial occlusion was noted. Cerebrovascular pathology was noted in 22% of cases, most commonly cerebrovascular atherosclerosis (10%). Conclusions: Cocaine-related deaths are a significant clinical problem in New South Wales.

A Fatal Overdose of Cocaine Associated with Coingestion of Marijuana, Buprenorphine, and Fluoxetine. Body Fluid and Tissue Distribution of Cocaine and Its Metabolites Determined by Hydrophilic Interaction Chromatography-Mass Spectrometry (HILIC-MS)

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

Gas chromatographic determination of cocaine and its metabolites in blood and urine from cocaine users in northwestern Spain.

A gas chromatographic method with fl ame ionization detection (GC/FID) was developed for the determination of cocaine and its metabolites in blood and urine samples from cocaine users in Northwestern Spain. After a solid-phase extraction with Bond Elut Certify cartridges and a derivatization with bis-trimethylsilyltrifluoroacetamide-trimethylchlorosilane (1%), calibration curves were constructed over 0.4-4 micro g ml(-1) for urine and 0.1-2 micro g ml(-1) for blood, using proadifen as the reference compound. The average extraction recoveries were 75% for urine and 78% for blood. The limits of detection and quantitation were 0.071 and 0.24 micro g ml(-1), respectively. Coefficients of variation were <10% and accuracy was within +/-12%. The average blood concentrations of cocaine, benzoylecgonine and ecgonine methyl ester in 42 living patients were 0.22, 1.43 and 0.16 micro g ml(-1), respectively. Urine samples were collected from individuals in the criminal justice system (70 cases), from drug abusers admitted to emergency rooms (36 cases) and from patients under detoxification treatment (36 cases). The second group exhibited the highest average concentrations (e.g. 0.97 micro g ml(-1) for cocaine, 5.23 micro g ml(-1) for benzoylecgonine and 0.39 micro g ml(-1) for ecgonine methyl ester). Sixty- five fatal intoxications due to cocaine alone or in combination with other drugs were studied, and average blood levels were found to be higher in the deaths related to cocaine alone (e.g. 0.40 micro g ml(-1) for cocaine, 2.38 micro g ml(-1) for benzoylecgonine and 0.38 micro g ml(-1) for ecgonine methyl ester).

Thoracic aortic dissection associated with cocaine abuse

Cardiovascular complications of cocaine abuse include myocardial ischemia and infarction, dysrhythmias, cardiomyopathies and aortic dissection.The case in point pertains to a 26-year-old, Caucasian male, substance abuser who suffered a thoracic aortic dissection following the use of crack cocaine.The autopsy and histological findings showed a connective tissue abnormality including a focal microcystic medial necrosis and a fragmentation of the elastic fibbers in the arterial walls.Blood concentrations of cocaine and benzoylecgonine, taken individually, were considered to be within a potentially toxic range.Blood concentrations of methadone also indicated use of this drug at the same time.The small amounts of morphine found in the blood and urine were compatible with heroine or morphine use more than 24h before death.

Cocaine Abstinence During Methadone Maintenance: Effects of Repeated Brief Exposure to Voucher-Based Reinforcement.

This study determined whether abstinence engendered by intermittent reinforcement might generalize to nonreinforced periods and enhance overall rates of cocaine abstinence among methadone maintenance patients. Participants were randomized to 1 of 3 groups. The quantitative group (n = 14) earned incentives for a 50% decrease in urine benzoylecgonine concentrations; the qualitative group (n = 13) earned incentives for providing urines with concentrations <300 ng/ml. Both reinforced groups received 12 random opportunities to earn 100 US dollars in vouchers for abstinence. The control group (n = 15) was encouraged to abstain on 12 occasions under the same schedule. Incentive participants achieved significantly more cocaine abstinence on earning than on nonearning days, with no difference between quantitative and qualitative groups. The study supports brief abstinence test efficacy but did not find that unpredictable opportunities to earn incentives generalized to nonreinforced days.

The pharmacology of cocaethylene in humans following cocaine and ethanol administration

Background: Concurrent use of cocaine and alcohol results in formation of a cocaine homolog and metabolite—cocaethylene. Methods: To characterize cocaethylene pharmacology, ten paid volunteer subjects were given deuterium-labeled (d 5) cocaine (0.3, 0.6, and 1.2 mg/kg and cocaine placebo) by a 15-min constant rate intravenous injection 1 h after a single oral dose of ethanol (1 g/kg) or ethanol and cocaine placebo using a double-blind, crossover design. Six of the same volunteers subsequently received a 1.2 mg/kg dose of cocaine alone. A small (7.5 mg) nonpharmacologically active dose of deuterium-labeled cocaethylene-d 3 was concurrently administered with the cocaine to enable calculation of absolute cocaethylene formation and clearance. Plasma and urine cocaine, cocaethylene, and benzoylecgonine concentrations, physiologic and subjective effects were measured. Results: When co-administered with ethanol, 17±6% (mean±S.D.) of the cocaine was converted to cocaethylene. Cocaethylene peak plasma concentrations and AUC increased proportionally to the cocaine dose. Ethanol ingestion prior to cocaine administration decreased urine benzoylecgonine levels by 48% and increased urinary cocaethylene and ecgonine ethyl ester levels. Subjects liked and experienced more total intoxication after the combination of cocaine and ethanol than after either drug alone. Conclusions: In the presence of ethanol, the altered biotransformation of cocaine resulted in 17% of an intravenous cocaine dose being converted to cocaethylene and relatively lower urinary concentrations of benzoylecgonine.

Use of High Performance Liquid Chromatography for the Determination of Cocaine and Benzoylecgonine in Human Hair

A high performance liquid chromatographic method involving diode array detection (HPLC–DAD) is proposed for the determination of cocaine and benzoylecgonine in human hair. Samples were washed, dried, and subjected to enzyme hydrolysis and liquid–liquid extraction in Toxitubes A® prior to analysis on a Nova‐Pak C18 (150 × 3.9 mm) column with a 70:30 (v/v) methanol–0.02 M phosphate buffer pH 7, at a constant flow‐rate of 0.4 mL/min as the mobile phase, and articaine as reference compound. The detector response was linear over the concentration range 2–200 ng/mg hair for both drugs. The detection and quantitation limits were 1 ng/mg and 2 ng/mg, respectively. The precision was quite acceptable, with coefficients of variation less than 5%. An overall 52 specimens from cocaine users were analysed with the proposed method and found to contain cocaine and benzoylecgonine concentrations over the ranges 4.2–554.7 ng/mg (average 57.3 ng/mg) and 0–1167.6 ng/mg (average 159.7 ng/mg), respectively.

Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases.

Carboxylesterases are important in the metabolism of cocaine, catalyzing the hydrolysis of cocaine to its two major metabolites, benzoylecgonine and ecgonine methyl ester. In the presence of ethanol, some cocaine undergoes transesterification with ethanol instead of hydrolysis with water producing the active metabolite, cocaethylene. The metabolic fate of cocaethylene is unknown, but given its structural similarity to cocaine, it was hypothesized that cocaethylene would also be metabolized by carboxylesterases and its elimination decreased in the presence of ethanol, as is cocaine's. Dogs were given cocaine alone, cocaethylene alone, cocaine and ethanol, cocaethylene and ethanol, and cocaine and cocaethylene on separate study days and sequential blood samples drawn. Plasma concentrations of cocaine, benzoylecgonine, and cocaethylene were determined by high-performance liquid chromatography. The pharmacokinetic dispositions of cocaine and cocaethylene were similar with clearance values of 0.91 +/- 0.22 and 0.79 +/- 0.16 l/min, and volumes of distribution of 2.6 +/- 0.82 and 2.7 +/- 0.47 l/kg, respectively. Both cocaine and cocaethylene clearances were decreased about 20% when given with ethanol. Following administration of cocaethylene alone, benzoylecgonine achieved similar plasma concentrations as those attained following cocaine alone, which indicates that benzoylecgonine is a major metabolite of cocaethylene. Carboxylesterases play an important role in the elimination of both cocaine and cocaethylene.

Urine Toxicology Samples in Cocaine Treatment Trials

How frequently should urine samples be collected and analyzed to accurately measure drug use in clinical trials of cocaine abuse treatments? Previous research suggests that analyzing one of three weekly urine toxicology samples in an opiate-related trial may be sufficient. To empirically address this question in the field of cocaine research, we examined the weekly variation in the cocaine metabolite benzoylecgonine (BE) concentration between pairs of weekly urine samples from a clinical trial of a treatment for cocaine dependence. Twice weekly urine samples from 71 subjects collected over eleven weeks were assayed for quantitative BE levels. Agreement between pairs of samples was estimated for both quantitative and qualitative measures of BE. Results indicated substantial intra-week variation with correlations never exceeding .50 and approximately 20% disagreement among samples using cutoff values in place of quantitative levels. Both samples, however, supported similar conclusions about group-level behavior.

Neonatal Hair Analysis for Benzoylecgonine: A Sensitive and Semiquantitative Biological Marker for Chronic Gestational Cocaine Exposure

Hair analysis for the major metabolite of cocaine, benzoylecgonine (BZE) was performed in a cohort of 251 predominantly African-American newborns utilizing a modified radioimmunoassay (RIA) (Abuscreen Roche Laboratories, Nutley, N.J., USA). Maternal drug intake was confirmed by positive urine drug screen for cocaine metabolites at the time of delivery. The BZE concentrations reported here are the composites of both the parent compound cocaine (hydrolyzed to BZE) and the native BZE metabolized by the patient and deposited in the hair follicle. Hair analysis as an indicator for gestational cocaine exposure had a sensitivity of 88%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 85%. The range of BZE was 99–23,300 ng/g of hair, with 79% having hair BZE levels <5,000 ng/g of hair. The BZE RIA was confirmed by gas chromatography and mass spectrometry (GC/MS). Of the 18 mother/infant pairs tested, the hair BZE ratio (maternal to neonatal) varied from 0.5 to 8.9 in 13 pairs. In spite of maternal high hair BZE levels, 5 newborns had no evidence of hair BZE, stressing the importance of the placental role for the cocaine transfer to the fetus. After controlling for gestational age, higher BZE levels significantly correlated with smaller head circumference (p < 0.03) and birth weight (p < 0.01).