Chronic administration of lipophilic drugs can result in accumulation and prolonged elimination during abstinence. It has been suggested that cocaine and/or metabolites can be detected in saliva and urine for an exten...
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Chronic administration of lipophilic drugs can result in accumulation and prolonged elimination during abstinence. It has been suggested that cocaine and/or metabolites can be detected in saliva and urine for an extended period following long-term, high-dose administration. The effects of chronic oral cocaine administration in healthy volunteer subjects with a history of cocaine abuse were investigated. Subjects were housed on a closed clinical ward and were administered oral cocaine in up to 16 daily sessions. In each session, volunteers received five equal doses of oral cocaine with 1 h between doses. Across sessions, cocaine was administered in ascending doses from an initial dose of 100 mg (500 mg/day) up to 400 mg (2 g/day), increasing by 25 mg/dose/session (125 mg/session). Participation in the study was terminated if cardiovascular safety parameters were exceeded. Plasma and saliva specimens were collected periodically during the dosing sessions and during the one-week withdrawal phase at the end of the study. All urine specimens were collected throughout the entire study. Specimens were analyzed for cocaine and metabolites by solid-phase extraction followed by gas chromatographic–mass spectrometric analysis in the SIM mode. The limit of detection for each analyte was approximately 1 ng/mL. The analytes measured included benzoylecgonine (BZE), ecgonine methyl ester, cocaine, benzoylnorecgonine, norcocaine, m- and p-hydroxycocaine, and m- and p-hydroxybenzoylecgonine. Noncompartmental analysis was employed for the determination of plasma and saliva pharmacokinetic parameters. Urinary elimination half-lives for cocaine and metabolites were determined by constructing ARE (amount remaining to be excreted) plots. Two phases of urinary elimination of cocaine and metabolites were observed. An initial elimination phase was observed during withdrawal that was similar to the elimination pattern observed after acute dosing. The mean (N = 6) plasma, saliva, and urine coc
A total of 30 human head-hair samples were analyzed for cocaine (COC), cocaethylene (CE), benzoylecgonine (BE), methylecgonine (EME), and norcocaine (NCOC) using a sensitive positive ion chemical ionization gas chroma...
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A total of 30 human head-hair samples were analyzed for cocaine (COC), cocaethylene (CE), benzoylecgonine (BE), methylecgonine (EME), and norcocaine (NCOC) using a sensitive positive ion chemical ionization gas chromatography–tandem mass spectrometry (GC–MS–MS) method. All 30 hair samples had been previously submitted to the laboratory and had confirmed positive for cocaine. Hair samples (20 mg each) were cut into small segments (2–5 mm) and incubated overnight at 45°C in 0.1N HCl after the addition of 50 μL of an internal standard mix of COC-d3 (1.0 ng/mg), BE-d3 (0.5 ng/mg), EME-d3 (0.25 ng/mg), and NCOC-3 (0.25 ng/mg). The samples were then extracted with Clean Screen? extraction columns from United Chemical Technologies, Inc. The final extract was evaporated to dryness and derivatized with 50 μL of 1,1,1,3,3,3-hexafluoro-2-propanol and 50 μL of trifluoroacetic anhydride at 90°C for 15 min. The derivatized samples were allowed to cool to room temperature, evaporated to dryness, and then reconstituted in 50 μL of ethyl acetate. Parent set masses (unbolded ions) and product ions were m/z 304 and m/z 182 and 82 (COC), m/z 307 and m/z 185 and 85 (COC-d3), m/z 318 and m/z 196 and 82 (CE), m/z 440 and m/z 318 and 105 (BE), m/z 443 and m/z 321 and 105 (BE-d3), m/z 296 and m/z 182, and 82 (EME), m/z 299 and m/z 185 and 85 (EME-d3), m/z 403 and m/z 386 and 105 (NCOC), m/z 406 and m/z 389 and 105 (NCOC-d3). Quantitation was accomplished by calculating the area ratio of the higher mass product ion (underlined ions) of analyte to the respective internal standard based on multilevel calibrations from 0.01 to 10.0 ng/mg. The GC–MS–MS method had a limit of detection of 0.01 ng/mg and a limit of quantitation of 0.05 ng/mg for all five analytes. COC, BE, and EME were detected in all 30 samples, and CE and NCOC were found in 19 and 29 samples, respectively. The average relative percentages of each metabolite normalized to the cocaine concentrations were 12.8%, 15.4%, 1.8%, and 2.5
Several reports suggest a prolonged elimination of cocaine and metabolites after chronic use compared with single or occasional use. This study was designed to measure the half-lives of cocaine in plasma and saliva of...
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Several reports suggest a prolonged elimination of cocaine and metabolites after chronic use compared with single or occasional use. This study was designed to measure the half-lives of cocaine in plasma and saliva of individuals who consumed cocaine on a frequent basis. The disposition and elimination patterns of cocaine and metabolites in the body fluids of chronic high-dose cocaine users during acute cessation of use were investigated. Plasma and saliva specimens were collected over a 12-h period during cessation and analyzed by gas chromatography–mass spectrometry. Pharmacokinetic parameters were derived by noncompartmental analysis of plasma and saliva data. Results indicated a cocaine terminal T1ú2 of 3.8 h in plasma and 7.9 h in saliva. The terminal T1ú2 of benzoylecgonine was 6.6 h in plasma and 9.2 h in saliva. Compared with prior studies of acute low-dose cocaine administration, these findings suggest that cocaine’s half-life is longer in active street users than in occasional users though the half-life of its main metabolite benzoylecgonine remains similar (as do cocaine saliva-to-plasma ratios). Thus, regular use of cocaine appears to alter the disposition and elimination of cocaine when compared to single or occasional use.
In this retrospective study, we examined the levels of cocaine and its major metabolites in plasma and urine from 29 randomly selected emergency department patients (19 males and 10 females, aged 19 to 55) whose urine...
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In this retrospective study, we examined the levels of cocaine and its major metabolites in plasma and urine from 29 randomly selected emergency department patients (19 males and 10 females, aged 19 to 55) whose urine screened positive for benzoylecgonine using fluorescence polarization immunoassay. Levels of cocaine along with benzoylecgonine, ecgonine methyl ester, and norcocaine were quantitated in EDTA plasma and urine from each patient using gas chromatography–mass spectrometry with selected ion monitoring. Admission diagnosis and history were also obtained for each patient. In plasma, the levels were 16–130 ng/mL for cocaine (n = 3), 27–96 ng/mL for ecgonine methyl ester (n = 9), and 18–1390 ng/mL for benzoylecgonine (n = 22). Norcocaine was not detected in any of the plasma samples. In urine, the concentration ranges were 4–40,130 ng/mL for cocaine (n = 23), 36–660,500 ng/mL for ecgonine methyl ester (n = 27), and 9–2520 ng/mL for norcocaine (n = 9). All urine samples were positive for benzoylecgonine (106–3,361,000 ng/mL), and benzoylecgonine was the only metabolite present in two urine samples (at concentrations of 407 and 435 ng/mL). Two patients had plasma and urine samples positive for all analytes (except norcocaine in plasma). The patient with the highest urinary concentrations of cocaine (40,130 ng/mL), ecgonine methyl ester (660,500 ng/mL), benzoylecgonine (3,361,000 ng/mL), and norcocaine (2520 ng/mL) had a small quantity of benzoylecgonine (465 ng/mL) in plasma. No correlation was noted with patient history, admitting diagnosis or symptomatology, or plasma/urine levels of cocaine or any of its metabolites.
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