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Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

269 records · Page 15Linked to original sources
PubMedDate not supplied

Incorporation of isotopically labeled cocaine and metabolites into human hair: 1. dose-response relationships.

Deuterium-labeled cocaine (cocaine-d5) was administered intravenously and/or intranasally in doses of 0.6-4.2 mg/kg to 25 human volunteers under laboratory clinical conditions. Sequential blood samples were collected for up to 3 days, and hair samples were collected for up to 10 months. Samples were analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine-d5 and its major metabolite, benzoylecgonine-d5 (BZE-d5). The parent drug, cocaine-d5, was the predominant analyte in hair, whereas BZE-d5 was the major analyte in blood, especially at later time periods. The amount of cocaine-d5 incorporated into hair ranged from 0.1 to 5 ng/mg hair, whereas the amount of BZE-d5 was approximately one-sixth of that concentration. The threshold dose for detection was estimated to be 25-35 mg of drug administered intravenously. A single dose could be detected for 2-6 months. Subjects receiving the same dose differed (from two to 12 times as much depending upon how it was measured) in the amount of cocaine-d5 incorporated into their hair. Non-Caucasians, in particular, incorporated more cocaine-d5 in hair than did Caucasians. Also, segmental analysis of the samples revealed considerable intersubject variability in the time drug first appeared in hair and the rate at which the drug moved along the hair shaft with time. These interindividual differences could not be explained by differences in plasma pharmacokinetics. Considered together, these results suggest that cocaine incorporation into hair may occur by way of multiple mechanisms--by way of sweat and sebum, for example--and at various times during the hair growth cycle. Thus, hair analysis using GC-MS appears to be a very sensitive method for detecting cocaine ingestion. However, within the range of doses used in the present study, hair does not provide a particularly accurate record of either the amount, time, or duration of drug use.

Administration, Intranasal↗
PubMedDate not supplied

Incorporation of isotopically labeled cocaine into human hair: race as a factor.

In order to evaluate race as a possible factor affecting the incorporation of drugs into human hair, 2 mg/kg deuterium-labeled cocaine (cocaine-d5) was administered intranasally to nine male non-Caucasian volunteers under controlled laboratory conditions. Sequential blood samples were collected for up to three days, and scalp hair samples were collected at 24 and 72 h after dosing and at monthly intervals for up to 12 months. The samples were then analyzed by gas chromatography-mass spectrometry for cocaine-d5 and benzoylegonine-d5 (BZE-d5). The amounts of cocaine-d5 found in the hair of these non-Caucasian subjects were compared with the amounts of cocaine-d5 found in the hair of Caucasian subjects who received the same cocaine dose under identical conditions as part of a study we reported previously. The non-Caucasians in the present study had approximately 2.7 times more cocaine-d5 in their hair than the Caucasian subjects in the earlier study. In five of the non-Caucasian subjects, cocaine-d5 could be detected in hair within 24 h after dosing. Curiously, we were unable to detect any cocaine-d5 in one of the non-Caucasian subject's hair at any time after dosing even though cocaine-d5 was in plasma at the expected levels. The results from these studies suggest there may be a racial bias in the incorporation of cocaine into human hair; however, the data are not conclusive because of the relatively small sample size.

Administration, Intranasal↗
PubMedDate not supplied

Cocaine metabolite kinetics in the newborn.

The study goal was to determine the half-life elimination of cocaine and benzoylecgonine (BZE) in the newborn. Three 0.3-mL blood samples were collected during the first day of life. Urine was collected once daily. Cocaine and BZE concentrations were determined by gas chromatography-mass spectrometry. An extraction method was developed for measuring low concentrations of cocaine and BZE in small (0.1 mL) blood samples. Cocaine had a half-life of 11.6 h in one subject. The half-life of BZE during the first day of life, based on blood data in 13 subjects, was 16 h (95% confidence interval [CI], 12.8 to 21.4 h). The half-life of BZE during the first week of life, based on urine data in 16 subjects, was 11.2 h (95% CI, 10.1 to 11.8 h). The novel extraction method for small blood sample volumes should be applicable to other basic drugs.

Chemistry Techniques, Analytical↗
PubMedDate not supplied

Sulfonium salts as derivatizing agents. 3. Quantitation of the cocaine metabolite benzoylecgonine in urine using gas chromatography with ion-pair extraction/on-column alkylation.

Recent studies have demonstrated the utility of quantitative assays for benzoylecgonine in assessing the efficacy of cocaine-dependence-treatment programs to determine if the amount of cocaine consumed has been reduced. We describe a simple gas chromatographic method for determining benzoylecgonine concentrations in urine. BZE is extracted from urine as an ion pair with tri-n-propylsulfonium ion. Injection into the heated injection port of the gas chromatograph results in thermal conversion of the ion pair to the n-propyl ester of BZE. Using the structural analogue of BZE, m-toluylecgonine, as the internal standard, the analysis is carried out on a (5% phenyl)methylpolysiloxane capillary column with nitrogen-phosphorus detection. There was a good correlation between BZE concentrations determined by gas chromatography-mass spectrometry and concentrations determined by the method described in this paper. Application to cocaine-dependence-treatment programs is discussed.

Alkylation↗
PubMedDate not supplied

Determination of methadone and its primary metabolite in biologic fluids using gas chromatography with nitrogen-phosphorus detection.

A method is described for the determination of methadone and its primary metabolite, 1,5-dimethyl-3,3-diphenyl-2-ethylidinepyrrolidine, in biologic fluids using gas chromatography with nitrogen-phosphorus detection. A simple extraction scheme is employed that is convenient for processing the large numbers of samples generated in pharmacokinetic studies. The method is sensitive enough for accurate determination of concentrations less than 5 ng/mL of both methadone and its primary metabolite in 1 mL of biologic specimens.

Chromatography, Gas↗
PubMedDate not supplied

Potential misrepresentation of 3,4-methylenedioxyamphetamine (MDA). A toxicological warning.

The illicit synthesis of the popular drug 3,4-methylenedioxyamphetamine (MDA) has frequently called upon the precursor piperonylacetone, which is reductively aminated with ammonium hydroxide. The term "piperonylacetone" has been used for two distinct chemical entities in the chemical literature, vis., 3,4-methylenedioxyphenylacetone or 3,4-methylenedioxybenzylacetone. It is only the first of these two chemicals which will give rise to MDA. The second chemical has been made commercially available as piperonylacetone and, employing the usual recipes, produces 1-(3,4-methylenedioxyphenyl)-3-aminobutane. This amine could be mistaken for MDA if only simple presumptive tests are employed. This latter base is largely unexplored pharmacologically and toxicologically and, as it may reasonably appear in illicit drug traffic misrepresented as MDA, it may well represent a clinical problem of unforseeable consequences.

3,4-Methylenedioxyamphetamine↗
PubMedDate not supplied

Disposition kinetics and metabolism of nicotine-1'-N-oxide in rabbits.

The disposition kinetics and metabolism of nicotine-1'-N-oxide (NNO) are of interest as the reduction of NNO might influence the pharmacokinetics of nicotine in tobacco users. The disposition kinetics of nicotine-1'-N-oxide were characterized in New Zealand rabbits. The clearance of NNO averaged 7.5 ml/min/kg. The half-life averaged 42.6 min and VDss was 0.34 liter/kg. The oral and ip bioavailabilities were 15.1 and 79%, respectively. NNO was reduced to nicotine and cotinine following i.v., oral, and ip injection. The pattern of metabolites after iv dosing suggests that there is systemic reduction of NNO, although the magnitude of that reduction is small, with less than 3% reduced to nicotine. Following oral NNO, 45% was reduced, with a metabolite pattern consistent with presystemic (bacterial or intestinal) metabolism.

Administration, Oral↗
PubMedDate not supplied

Viral hepatitis.

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Carrier State↗