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Biomedical subjects

E J Cone

Publications and source records attributed to E J Cone.

At least 55 records · Page 3Linked to original sources
PubMed1996

Sustained cocaine abstinence in methadone maintenance patients through voucher-based reinforcement therapy.

BACKGROUND: Chronic cocaine abuse remains a serious and costly public health problem. This study assessed the effectiveness of a voucher-based reinforcement contingency in producing sustained cocaine abstinence. METHODS: A randomized controlled trial compared voucher-based reinforcement of cocaine abstinence to noncontingent voucher presentation. Patients were selected from 52 consecutively admitted injecting heroin abusers in a methadone maintenance treatment program. Patients with heavy cocaine use during baseline period (N = 37) participated. Except where otherwise indicated, the term cocaine abuse is used in this article in a generic sense and not according to the DSM-III-R definition. Patients exposed to abstinence reinforcement received a voucher for each cocaine-free urine sample (ie, negative for benzoylecgonine) provided three times per week throughout a 12-week period; the vouchers had monetary values that increased as the number of consecutive cocaine-free urine samples increased. Control patients received noncontingent vouchers that were matched in pattern and amount to the vouchers received by patients in the abstinence reinforcement group. RESULTS: Patients receiving vouchers for cocaine-free urine samples achieved significantly more weeks of cocaine abstinence (P = .007) and significantly longer durations of sustained cocaine abstinence (P = .001) than controls. Nine patients (47%) receiving vouchers for cocaine-free urine samples achieved between 7 and 12 weeks of sustained cocaine abstinence; only one control patient (6%) achieved more than 2 weeks of sustained abstinence. Among patients receiving vouchers for cocaine-free urine samples, those who achieved sustained abstinence ( > or = 5 weeks) had significantly lower concentrations of benzoylecgonine in baseline urine samples than those who did not achieve sustained abstinence (P < or = .01). Patients receiving voucher reinforcement rated the overall treatment quality significantly higher than controls (P = .002). CONCLUSION: Voucher-based reinforcement contingencies can produce sustained cocaine abstinence in injecting polydrug abusers.

Adult↗
PubMed1996

In vitro binding studies of drugs to hair: influence of melanin and lipids on cocaine binding to Caucasoid and Africoid hair.

Although the mechanism(s) of drug deposition in hair are unknown, there is evidence that suggests that the amount and type of melanin present are major factors in determining how much drug enters hair after exposure. The role of other hair components, such as lipids, has received less attention. We used in vitro binding techniques to evaluate the binding of radiolabeled cocaine to different types of treated and untreated hair specimens. Divided male and female Caucasoid (black/brown and blond colored) and Africoid (black colored) hair specimens (N = 7) were exhaustively extracted to remove lipid components (lipid-extracted hair). Separate portions were bleached to denature or alter melanin content. Experiments with radiolabeled cocaine were performed on untreated, lipid-extracted, and bleached portions of hair from different groups. Cocaine binding was significantly higher (p < .01) to male Africoid hair compared with other groups. The amount of drug binding was similar among female Africoid and male and female, black/brown Caucasoid specimens. The lowest amount of binding was observed with blond, female Caucasoid specimens. Binding experiments also revealed that specific cocaine binding generally did not differ significantly between lipid-extracted hair and untreated hair, but bleaching of most hair specimens resulted in significant (p < .01) decreases in specific binding compared with untreated hair. In separate experiments with cocaine-treated hair specimens, digested samples were evaluated to determine if removal of the insoluble melanin fraction from soluble hair components provided a means of normalization of drug content and elimination of color bias. Removal of the insoluble melanin fraction was not effective in removal of significant amounts of cocaine, which indicated that the digestion process released bound cocaine into the digest solution. Overall, these experiments suggested that lipids in hair play a minor role in drug binding, whereas melanin functions as a major binding site for cocaine. Natural (ethnic) or artificial (bleaching) differences in melanin content may determine the extent of cocaine entrapment in hair after drug exposure. Further, digestion of hair samples and removal of insoluble melanin failed to be effective in removal of hair color bias.

Analysis of Variance↗
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

Urinary excretion profiles of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol in humans after single smoked doses of marijuana.

Interpretation of marijuana-positive urine tests requires an understanding of the excretion pattern of marijuana metabolites in humans. However, limited urinary excretion data from controlled clinical studies of marijuana use are available. In this study, six subjects smoked a single marijuana cigarette (placebo, 1.75% delta 9-tetrahydrocannabinol [THC], or 3.55% THC) each week while residing on the clinical ward of the Addiction Research Center. Individual urine specimens were collected for 7 days after drug administration and analyzed for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GC-MS) with a limit of detection of 0.5 ng/mL. Substantial intersubject variability in patterns of THCCOOH excretion was noted between subjects and between doses. Mean THCCOOH concentrations in the first urine collections were 47 +/- 22.3 ng/mL and 75.3 +/- 48.9 ng/mL after the 1.75 and 3.55% THC cigarettes, respectively. Mean peak urine THCCOOH concentrations averaged 89.8 +/- 31.9 ng/mL and 153.4 +/- 49.2 ng/mL after smoking of approximately 15.8 mg and 33.8 mg THC, respectively. The mean times of peak urine concentration were 7.7 +/- 0.8 h after the 1.75% THC and 13.9 +/- 3.5 h after the 3.55% THC dose. Mean GC-MS THCCOOH detection times for the last positive urine sample after the smoking of a single 1.75 or 3.55% THC cigarette were 33.7 +/- 9.2 h and 88.6 +/- 9.5 h, respectively, when a 15-ng/mL cutoff concentration was used. An average of 93.9 +/- 24.5 micrograms THCCOOH (range, 34.6-171.6 micrograms) was excreted by each subject during the 7-day period after smoking of a single 1.75% THC cigarette. The average amount of THCCOOH excreted in the same time period after the high dose was 197.4 +/- 33.6 micrograms (range, 107.5-305.0 micrograms). This represented an average of only 0.54 +/- 0.14% and 0.53 +/- 0.09% of the original amount of THC in the low-and high-dose cigarettes, respectively. These data provide a detailed complication of THCCOOH concentrations in urine after administration of marijuana that may aid in the interpretation of urine cannabinoid results.

Adult↗
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↗
PubMed1996

Mechanisms of drug incorporation into hair.

Hair testing for drugs of abuse is a developing technology that offers the possibility of longer detection times than is commonly obtained with urine or blood analysis. There are many uncertainties concerning how drugs enter hair and factors that affect drug deposition and residence in hair. Possible routes of drug entry include diffusion from blood, sweat, sebum, and skin and entry from the environment. Evidence is reviewed regarding the importance of each of these routes as possible contributors to drug deposition in hair. Binding to specific sites in hair may involve both electrostatic forces and weaker attractions, such as van der Waals forces. Melanin and protein constituents of hair may serve as binding sites. Recent in vitro studies suggest that the color of hair or melanin content may be the major determinant of cocaine binding and, consequently, may result in color or ethnic bias in hair testing.

Hair↗
PubMed1996

Incorporation of codeine and metabolites into hair. Role of pigmentation.

Xenobiotics circulating in the blood may become incorporated into growing hair. Melanin has affinity for many pharmacologically unrelated drugs and is responsible for the pigmentation in hair. To assess the role of pigmentation in the incorporation of drugs into hair, the distribution of codeine and its metabolites was studied in Sprague-Dawley (SD; white nonpigmented hair), Dark Agouti (DA; brown pigmented hair), and hooded Long-Evans (LE; both black pigmented and white nonpigmented hair) rats. Codeine was administered at a dose of 40 mg/kg/day i.p. for 5 days. Fourteen days after beginning the dosing protocol, hair was collected and analyzed for codeine, and its metabolite, morphine, by positive-ion chemical ionization GC/ion-trap MS. The plasma pharmacokinetics for codeine and morphine were also determined after a single 40 mg/kg injection (equivalent to first dose in 5-day dosing protocol) in all three strains of rats. Hair and plasma codeine and morphine concentrations were also determined after acid hydrolysis to evaluate the presence of glucuronide metabolites. Codeine concentrations in the hair of SD, DA, and pigmented LE hair were 0.98 +/- 0.10, 5.99 +/- 1.24, and 111.93 +/- 18.69 ng/mg hair, respectively; morphine concentrations were 0.34 +/- 0.04, 0.51 +/- 0.11, and 14.46 +/- 1.81 ng/mg hair, respectively; morphine glucuronide concentrations were 0.67 +/- 0.08, 1.04 +/- 0.37, and 13.80 +/- 3.60 ng/mg hair, respectively. Studies examining the in vitro binding of [3H] codeine and [3H]morphine to hair demonstrated both specific and nonspecific binding sites for codeine and morphine. Pigmented hair from LE rats possessed the greatest number of binding sites, white hair from SD rats contained the least, and brown hair from DA rats was intermediate. A time course study of codeine and its metabolites showed pigment-mediated differences in incorporation of codeine and metabolites within a few hours of drug administration. These data indicate that pigmented hair possesses a greater capacity to bind and incorporate codeine and its metabolites than does nonpigmented hair. Interpretation of hair concentrations of drugs should involve consideration of hair pigmentation.

Animals↗
PubMed1996

Arterial and venous cocaine plasma concentrations in humans: relationship to route of administration, cardiovascular effects and subjective effects.

Arterial plasma drug concentrations should be a strong predictor of resultant physiological and behavioral effects of smoked drugs. Nine healthy male volunteers, who were current users of smoked and i.v. cocaine, participated in a study directly comparing arterial and venous cocaine plasma concentrations after smoked and i.v. cocaine. Each volunteer was first tested under all dosing conditions without an arterial catheter (phase I), to determine whether subjects could tolerate each cocaine dose, before testing with an arterial catheter (phase II). Phase II consisted of two test days, each consisting of either four smoked-cocaine sessions (sham, 12.5, 25 and 50 mg) or four i.v. cocaine sessions (0, 8, 16 and 32 mg) in ascending order, spaced 90 min apart. For the two highest doses for each route, arterial and venous blood samples were taken simultaneously before drug administration, during drug administration and frequently after drug administration. At the same time, cardiovascular effects and subjective effects were measured. Arterial cocaine concentrations were substantially higher than venous cocaine concentrations after both routes of cocaine administration. After either smoked or i.v. cocaine, maximal arterial cocaine concentrations occurred within 15 sec, whereas maximal venous cocaine concentrations occurred within 4 min. The onset of cardiovascular and subjective effects was also rapid, and arterial cocaine concentrations tended to account for these effects to a greater extent than did venous cocaine concentrations. Even though arterial and venous cocaine concentrations were lower after smoked cocaine, compared with i.v. cocaine, the magnitudes of cardiovascular and subjective effects were similar, suggesting that smoked cocaine may produce a greater effect at similar concentrations. These findings do not support the hypothesis that the greater effects observed after smoking are a result of smoked cocaine reaching the brain faster than i.v. cocaine as measured by peripheral arterial plasma concentrations.

Adult↗
PubMed1995

Testing human hair for drugs of abuse. IV. Environmental cocaine contamination and washing effects.

Active cocaine use results in sequestration of parent drug in hair. In addition, hair has unique physicochemical properties that permit absorption of cocaine from the environment. When hair is tested for evidence of cocaine, it is important to consider whether the positive test resulted from active drug use or environmental contamination. In a series of laboratory experiments, it was found that exposure of 'cut' hair to cocaine vapor ('crack' smoke) and to aqueous solutions of cocaine hydrochloride resulted in significant contamination of hair samples. Similar results were obtained with two subjects who were exposed to cocaine vapor in an unventilated room. The amount of contamination adsorbed by hair depended upon both time and extent of exposure. Washing the hair samples with methanol removed > 70% of the cocaine contaminant after cocaine vapor exposure, but was less effective (< 50%) following contamination with aqueous cocaine. Shampoo treatment cycles (overnight soaking) progressively removed increasing amounts of cocaine from the contaminated hair, but residual cocaine remained after 10 cycles. Studies were also performed to determine the usefulness of benzoylecgonine as a marker of active cocaine administration. Small amounts of benzoylecgonine (ca. 1 ng/mg) were formed in hair as a result of environmental contamination with cocaine. Also, it was found that benzoylecgonine could be adsorbed from illicit cocaine contaminated with benzoylecgonine. It was concluded that positive hair test results should be interpreted cautiously due to the possibility of environmental contamination from cocaine and related constituents.

Air Pollution↗
PubMed1995

Comparison of heroin and cocaine concentrations in saliva with concentrations in blood and plasma.

Saliva is an alternate biological matrix for drug testing that has several advantages over more traditional fluids such as blood and urine. Collection is rapid, noninvasive, and relatively easy to obtain. Several reports have detailed the appearance of drugs of abuse in saliva, but few have compared the excretion profiles of drugs administered by different routes. In this study, subjects were administered three smoked and three intravenous doses of heroin in an ascending dose design. Blood and saliva were collected periodically after drug administration and analyzed by gas chromatography-mass spectrometry (GC-MS) for heroin, 6-acetylmorphine, and morphine. In a second study, subjects were administered a single, smoked dose of 40 mg cocaine base and an intravenous dose of 44.8 mg cocaine HO on separate occasions. Plasma and saliva were collected and analyzed by CC-MS for cocaine, anhydroecgonine methyl ester (AEME), and seven additional metabolites. Heroin and 6-acetylmorphine were detected in the first saliva sample collected (2 min) following drug administration by both routes. Peak heroin concentrations were achieved quickly, between 2 and 5 min after intravenous administration and at 2 min after smoke heroin. Peak heroin concentrations in saliva after smoking heroin base ranged from 3534 (2.6 mg) to 20,580 ng/mL (5.2 mg), and after intravenous administration, concentrations ranged from 6 (10 mg heroin HCl to 30 ng/mL (12 mg heroin HCl. Saliva concentrations of heroin declined rapidly after intravenous administration, reaching the limit of sensitivity of the assay (1 ng/mL) by 60 min. Heroin concentrations in saliva after smoking declined slowly; detection times ranged from 4 to 24 h. Cocaine was the major analyte detected in saliva and plasma after smoked and intravenous administration. Peak saliva cocaine concentrations after intravenous administration ranged from 428 to 1927 ng/mL (N = 7); after smoking, they ranged from 15,852 to 504,880 ng/mL (N = 7). Peak plasma cocaine concentrations after intravenous administration ranged from 122 to 442 ng/mL A = 7), and after smoking, concentrations ranged from 46 to 291 ng/mL A = 7). The thermal degradation product of cocaine, AEME, was detected in saliva but not in plasma after smoking. Peak saliva AEME concentrations were achieved at 2 min and ranged from 558 to 4374 ng/mL (N = 7). These are the first reported observations of heroin and metabolites in saliva following heroin smoking and of AEME in saliva after smoking cocaine base. The presence of AEME in saliva may be useful as a marker of the smoked route following cocaine administration.

Administration, Inhalation↗
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↗
PubMed1995

Detection times of marijuana metabolites in urine by immunoassay and GC-MS.

Reports of prolonged drug excretion have provided the basis for the common assumption that cannabinoid metabolites may he detected in urine for a week or longer. The accuracy, sensitivity, and specificity of immunoassays for the detection of cannabinoids and metabolites are unique for a specific assay and may change overtime. it is important that individuals who select assays and those who interpret test results be aware of qualitative and quantitative changes that occur. In the present study, detection times of cannabinoids in urine were determined using cannabinoid immunoassays with 20-, 50-, and 100-ng/mL cutoffs and using gas chromatography-mass spectrometry (GC-MS). Six subjects each smoked a single marijuana cigarette (placebo, 1.75, or 3.55% delta9-tetrahydrocannabinol [THC]) each week while residing on the clinical ward of the Addiction Research Center. Each urine specimen was analyzed under blind conditions by immunoassay according to the manufacturer's instructions. The following cannabinoid reagents were evaluated: EMIT d.a.u. 100, EMIT d.a.u. 50, EMIT d.a.u. 20, EMIT II 100, EMIT II 50, Abuscreen OnLine, and Abuscreen RIA, DRI, and ADx. All urine specimens were also analyzed for 11-nor-9-carboxy-delta9-THC by GC-MS using a 15-ng/mL cutoff. Urinary cannabinoid detection times varied substantially across assays, subjects, doses, and cutoff concentrations. Detection times were shorter than previously assumed. Mean detection times increased from a maximum of 0.5 days after the low dose to 1.5 days after the high dose using the 100-ng/mL cutoff. Mean detection times were less than 1 day following the low dose and less than 2 days following high-dose exposure using the 50-ng/mL cutoff. Mean detection times ranged from 1 to 5 days after the low dose and from 3 to 6 days after the high dose using the 20-ng/mL cutoff immunoassay. GC-MS detection times were approximately twice as long as mean detection times using an immunoassay with a cutoff of 50 ng/mL. Differences in sensitivity and specificity between the available immunoassay products affected the efficiency of detection of marijuana use. These results indicate that recent reductions in cannabinoid cutoffs by military and federally mandated programs will increase detection times and improve sensitivity, as expected. However, monitoring acute marijuana usage with a commercial cannabinoid immunoassay that has a 50-ng/mL cutoff concentration provides only a narrow window of detection of 1-2 days.

Adult↗
PubMed1995

Pharmacokinetics and pharmacodynamics of cocaine.

A dramatic shift has occurred over the last decade in the route of cocaine administration by drug abusers in the United States. The favored route has changed from intranasal and intravenous use to administration of cocaine ("crack") by the smoking route. The reasons for this shift are not well understood but may include social and environmental factors such as the ease and convenience of the smoking route, avoidance of needle-transmitted disease, and possible pharmacological differences produced by the different routes of administration. This study examined the influences exerted by changes in the route of administration on pharmacokinetic parameters and drug-induced behavioral and physiological effects of cocaine. Six male subjects who provided informed consent and had a recent history of cocaine use by the intravenous and smoked routes participated in a blind, double-dummy, crossover study conducted on a clinical research ward. On different occasions, subjects received single doses of cocaine by the intravenous (25 mg, cocaine HCl), intranasal (32 mg, cocaine HCl), and smoked (42 mg, cocaine base) routes. Physiological and behavioral measures were collected prior to and periodically after drug administration. Concurrent blood samples were collected and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry, Plasma concentrations of cocaine and benzoylecgonine were fitted to pharmacokinetic models by nonlinear regression analysis. Behavioral measures of "good" drug effects and "liking" were higher by the smoked route than the intravenous route, but physiological changes were approximately equal at equivalent plasma concentrations of cocaine. Intranasal cocaine administration was characterized by lower cocaine plasma concentrations and a slower onset of pharmacological effects that were generally of lesser magnitude than those observed by other routes of administration. Overall, this study demonstrated that cocaine administration by the smoked route produced substantially higher behavioral responses than an equivalent dose of cocaine administered by the intravenous route. This finding suggests that smoked cocaine (crack) has a higher abuse liability and greater dependence-producing properties than equivalent doses of cocaine administered by the intravenous or intranasal route.

Administration, Inhalation↗
PubMed1995

Selecting an appropriate isotopic internal standard for gas chromatography/mass spectrometry analysis of drugs of abuse--pentobarbital example.

Internal standards are commonly used for the quantitative determination of drugs of abuse and their metabolites (drug/metabolite) in biological fluids and tissues by the selective ion monitoring (SIM) gas chromatography/mass spectrometry (GC/MS) procedure. Analogs of drugs/metabolites that are labeled with three or more deuterium atoms (isotopic analog) at appropriate positions are considered to be the most effective internal standards for these applications. Before a specific deuterated analog can be adopted as an internal standard in a GC/MS assay, the mass spectrum of the compound or its derivative must be evaluated along with the corresponding spectrum from the parent drug/metabolite. There should be an adequate number of sufficiently high-mass ions (typically three for the drug/metabolite and two for the isotopic analog) that can be attributed to each analyte, and these ions should be sufficiently free of interference from the other analyte of the pair (cross-contribution). Interferences may be caused by the presence of an isotopic impurity in the deuterated analog (extrinsic factor) or may be due to the ion fragmentation characteristics of the compound (intrinsic factor). The extrinsic factor may be corrected by the manufacturer with different synthetic methods and purification procedures, while the intrinsic factor may be partially or wholly corrected through the use of different chemical derivatives (sample preparation stage) or different ionization (GC/MS assay stage) procedures. In this study, pentobarbital/d5-pentobarbital is used as the exemplar analyte/deuterated analog pair to illustrate the ion selection and evaluation procedures. Full-scan mass spectra were employed for preliminary ion selection. SIM data were then used to calculate the extent, if any, of cross-contributions.(ABSTRACT TRUNCATED AT 250 WORDS)

Gas Chromatography-Mass Spectrometry↗
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

Confirmatory tests for drugs in the workplace by gas chromatography-mass spectrometry.

The Mandatory Guidelines for Federal Workplace Drug Testing Programs require the use of gas chromatography-mass spectrometry (GC-MS) for the confirmation of presumptive positive urine specimens. This review focuses upon GC-MS methods developed specifically for forensic confirmation of amphetamine, methamphetamine, 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-acid), benzoylecgonine, morphine, codeine and phencyclidine in urine for purposes of workplace drug testing. In addition, current laboratory issues pertaining to each drug class are reviewed. Generally, drug assays utilized either liquid-liquid or solid-phase extraction methods, derivatization if necessary, and GC-MS detection operating in the selected ion monitoring mode or by full scan acquisition.

Amphetamines↗