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Biomedical subjects

T Lutz

Publications and source records attributed to T Lutz.

At least 37 records · Page 2Linked to original sources
PubMed1989

Mass spectrometric studies of cocaine disposition in animals and humans using stable isotope-labeled analogues.

Ion cluster technique in conjunction with gas chromatography-mass spectrometry (GC-MS) was used for the identification and quantitation of major metabolites of cocaine (1a) in rat and humans. In a typical experiment, a female rat weighing 250 gm was intraperitoneally administered a 20-mg/kg mixture of 1a, NCD3-cocaine (1b), OCD3-cocaine (1c), and 4T2-cocaine (1d). The urine was collected, extracted with organic solvents, and separated into several fractions using TLC and HPLC techniques. Tritium radioactivity in a metabolically stable position in 1d was useful in the separation of metabolites, while the deuterium labeled 1(b + c), creating an artificial isotopic cluster, provided specific identification of metabolites by mass spectrometric interpretation. Norcocaine (2), benzoylnorecgonine (3), N-hydroxynorcocaine (4), methylecgonidine (5), benzoylecgonine (11), ecgonine methyl ester (9), hydroxycocaine (7), hydroxymethoxycocaine (10), and dimethoxyhydroxycocaine (6) were found to be the major metabolites of 1a in the rat urine as well as in plasma. The whole brain analysis showed significant amounts of unmetabolized 1a and 2, and minor concentrations of 9, 5, 7, and 10, and traces of 6. Some of these metabolites have been reported earlier by us as well as other investigators and are unequivocally confirmed in this work. Unmetabolized 1a, its pharmacologically active metabolite 2, and other major metabolites were quantitated in the rat brain, plasma, and urine using stable isotope-labeled analogues as internal standards and selected ion monitoring (SIM) mass spectrometry. The pharmacokinetic profiles of 1a and 2 indicate half-lives of less than 20 min in the brain and plasma. These data are in good agreement with widely reported short-lived behavioral effects of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Metabolism and pharmacokinetics of phenelzine: lack of evidence for acetylation pathway in humans.

Earlier studies have suggested that patients with slow acetylation phenotype were more likely to respond to phenelzine treatment and more likely to experience side effects. The metabolism of phenelzine has not been extensively investigated in humans because of limitations in analytical methodology. A labeled form of phenelzine is required for metabolite identification because these same compounds can arise from endogenous substances e.g., phenylacetic acid. The use of a stable isotope-labeled compound has the advantage that in vivo studies can be performed without radiation exposure. Site-specific, stable isotope-labeled phenelzine analogs were synthesized and used in metabolic and pharmacokinetic studies in humans. The authors were unable to detect N-acetylphenelzine in any urine or plasma samples. The major metabolites phenylacetic acid and parahydroxyphenylacetic acid constitute up to 79% of the administered dose excreted via the urine in the first 96 hours. These studies indicate that N-acetylation of phenelzine is not a significant metabolic pathway in humans, which helps explain recent clinical studies that failed to find an association between acetylation phenotype and clinical effects of phenelzine.

Acetylation↗
PubMed1981

A stable isotope dilution assay for the antiparkinsonian drug benztropine in biological fluids.

A quantitative gas chromatographic-mass spectrometric (GC-MS) assay was developed for the determination of benztropine in human urine and plasma. The assay utilizes selected ion focusing to monitor in a GC effluent a specific fragment ion of benztropine generated by electron-impact ionization. Benztropine-d3 was the internal standard. The assay can measure 5 ng/ml of benztropine/ml with about 6% precision. The curve relating the amounts of benztropine added versus the amounts found over a large range of benztropine concentrations was a straight line with a nearly zero intercept and a slope of 0.98 +/- 0.02. The method was used for the analysis of benztropine in urine and plasma of patients on therapeutic dose of the drug.

Benztropine↗
PubMed1980

Determination of phenelzine in human plasma with gas chromatography-mass spectrometry using an isotope labeled internal standard.

A quantitative gas chromatographic-mass spectrometric assay was developed for the determination of phenelzine in human plasma. Phenelzine, in aqueous solution or in plasma reacts at room temperature with pentafluorobenzaldehyde to form quantitatively a hydrazone derivative. The derivative has good gas chromatographic characteristics. The assay utilizes selected ion monitoring in a gas chromatographic effluent, the molecular ion generated by electron impact ionization of phenelzine derivative. Phenelzine-d, was synthesized and used as an internal standard. The assay can measure 2 ng/ml of the drug with about 10% precision. The method was used for the determination of steady state levels of phenelzine in the plasma of patients taking a therapeutic dose of the drug.

Deuterium↗
PubMed1980

GLC-mass spectrometric determination of maprotiline and its major metabolite using stable isotope-labeled analog as internal standard.

A quantitative GLC-mass spectrometric assay was developed for the determination of maprotiline and its major metabolite, desmethylmaprotiline, in animal and human plasma. The assay utilizes selective-ion focusing to monitor, in a GLC effluent, the fragment ions and the base peaks of maprotiline and desmethylmaprotiline trifluoroacetamides generated by electron-impact ionization. Maprotiline-d3 was the internal standard. The assay can measure 2 ng of maprotiline (and the metabolite)/ml of plasma with approximately 5% precision. The curves relating the amounts of maprotiline and the metabolite added versus the amounts experimentally found over a large concentration range were linear with nearly zero intercepts and slopes of 0.99 +/- 0.01 and 0.98 +/- 0.02, respectively. The method was used to study the pharmacokinetic pattern of the drug in rabbits as well as to analyze intact maprotiline and the metabolite in patients maintained on therapeutic doses of maprotiline. Assay specificity was confirmed by complete consistency of the mass spectra of maprotiline and desmethylmaprotiline with those of the authentic materials.

Animals↗
PubMed1980

The efficacy of triazolam and chloral hydrate in geriatric insomniacs.

A double-blind crossover study was performed to evaluate the efficacy of hypnotics in geriatric insomniacs. Twenty-seven patients with a mean age of 70 years (range 60-94 years) received each of five treatments on 5 consecutive nights. The treatment conditions, consisting of chloral hydrate 250 and 500 mg, triazolam 0.25 and 0.50 mg, and placebo, were administered using a Latin Square design. Subjective estimates of sleep were collected in the morning following each treatment night. The patients' global evaluation of effectiveness indicated that triazolam 0.25 mg and 0.50 mg improved sleep more than placebo, while chloral hydrate 250 and 500 mg were not better than placebo. Triazolam 0.50 mg was felt to be significantly better than either dose of chloral hydrate. In addition, triazolam 0.50 mg was found to significantly decrease the patients' estimates of their sleep latency. Patients estimated their total sleep time to be longer following the use of triazolam 0.25 mg as compared to choral hydrate 500 mg, and their estimates of the number of awakenings was significantly lower on triazolam 0.50 mg than it was on chloral hydrate 500 mg or placebo.

Aged↗
PubMed1978

Mass spectrometric determination of cocaine and its biologically active metabolite, norcocaine, in human urine.

A gas chromatographic mass spectrometric assay has been developed for the determination of cocaine and its pharmacologically active metabolite, norcocaine, in human urine. [2H3]Cocaine and [2H3]norcocaine were used as internal standards. The assay utilizes selective focusing to monitor in a gas chromatographic effluent the molecular ions of cocaine, [2H3]cocaine and the fragment ions of trifluoroacetylated norcocaine, [2H3]norcocaine generated by electron impact ionization. The assay can measure 2 ng ml-1 each of cocaine and norcocaine with about 5% precision. The curves, relating the amounts of cocaine and norcocaine added to control urine per 'fixed' amounts of their labeled analogs, versus the appropriate ion intensity ratios are straight lines with nearly zero intercepts and slopes of 0.98 +/- 0.01 and 0.98 +/- 0.02, respectively. The methodology is used for the analysis of urinary cocaine and norcocaine from three human subjects who received 100 mg cocaine-HCL intravenously.

Cocaine↗
PubMed1978

Mass fragmentographic determination of methadyl acetate in urine using stable isotope labeled analog as internal standard.

A quantitative GLC-mass spectrometric assay was developed for the determination of methadyl acetate in urine. The assay utilized selective ion focusing to monitor, in a GLC effluent, the M--15 ion generated by electron-impact ionization of methadyl acetate. Methadyl acetate-d4 was used as an internal standard. The assay can measure 10 ng of drug/ml with about 6% precision. The curve relating the amounts of drug added to control urine versus the amounts experimentally found over a large concentration range is a straight line with a slope of 0.98 +/- 0.02 and a nearly zero intercept. Assay specificity was confirmed by complete identity of the mass spectrum of methadyl acetate in the biological extract with that of the authentic material. The method was used for the urinary analysis of methadyl acetate in a rabbit given a single intravenous dose. The animal excreted less than 1% of the intact drug with a half-life of approximately 15 hr. Consequently, the long-acting characteristic of methadyl acetate must be attributed to its metabolism into active metabolites.

Animals↗
PubMed1976

Intermediate use of triazolam: a sleep laboratory study.

The present study was undertaken to evaluate the intermediate effects of triazolam 0-5 mg on the sleep of insomniac patients. The results showed that triazolam is effective in inducing and maintaining sleep without producing any major effects on sleep staging. Triazolam did not lead to significant subjective complaints or any deterioration in the physical condition of the patients. The effectiveness of traizolam did not vary over a two-week period.

Adult↗
PubMedDate not supplied

Ion cluster techniques in drug metabolism: use of a mixture of labeled and unlabeled cocaine to facilitate metabolite identification.

Cocaine disposition studies in the rat are described. A mixture of cocaine, cocaine-d3, cocaine-14C, and cocaine-3H was used as a dose. The urine was collected, extracted with organic solvents, and fractions collected using HPLC and TLC. The radioactive cocaine was useful in the separation of metabolites while the deuterium-labeled cocaine, creating an artificial isotopic cluster, provided specific identification of the metabolites by gas chromatography/mass spectrometry. Benzoylecgonine, ecgoninemethylester, ecgonidine, norcocaine, N-hydroxynorcocaine, hydroxycocaine, and hydroxymethoxycocaine were found to be the major metabolites, while ecgonine, benzoylnorecgonine, and cocaine-N-oxide seemed to be present in trace amounts. Dimethoxyhydroxy cocaine was tentatively identified. Several of these newly identified metabolites of cocaine were present in significant concentrations and could contribute to the toxic effects of cocaine.

Animals↗