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Biomedical subjects

M G Horning

Publications and source records attributed to M G Horning.

At least 19 recordsLinked to original sources
PubMed1987

Metabolism of bromobenzene. Analytical chemical and structural problems associated with studies of the metabolism of a model aromatic compound.

Our studies of bromobenzene metabolism have shown that the 3,4-oxide is metabolized to 3- and 4-bromophenol through an extended glutathione pathway. The mechanism of sulfur elimination from a dihydrobromobenzene metabolite is not known, although it is known that the aromatization reaction will occur in a 9000-g supernatant fraction of rat liver. The hepatotoxic and nephrotoxic metabolites of bromobenzene are most likely bromthiocatechols and a bromothiopyrogallol, respectively.

Animals↗
PubMed1987

Analytical methods for the study of urinary thioether metabolites in the rat and guinea pig.

Methods are described for the isolation and identification of three classes of bivalent sulfur metabolites characterized as neutral methylthio ethers, ethyl acetate-soluble acidic thioethers and ethyl acetate-insoluble acidic thioethers from rat and guinea pig urine. After extraction of the metabolites by the ammonium carbonate-ethyl acetate procedure, the individual metabolites are separated by capillary gas chromatography and/or by high-performance liquid chromatography with both mu Bondapak C18 and Porasil columns. Identification of the metabolites is based on gas chromatography-mass spectrometry (electron impact) and on fast atom bombardment mass spectrometry. Interesting species differences in metabolism were observed. The major ethyl acetate-soluble acidic thioethers in rat urine are mercapturic acids. In contrast, in the guinea pig a new pathway involving mercaptopyruvic, mercaptolactic and mercaptoacetic acids is operative. The thioether metabolites of styrene oxide and phenanthrene are described, but the procedures have been applied in studies of several drugs and environmental chemicals in our laboratory.

Animals↗
PubMed1978

Metabolism of biphenyl in the rat.

The metabolism of biphenyl in the rat has been studied by using gas chromatographic and mass spectrometric methods. The free and conjugated urinary metabolites were characterized. Eight new metabolites were isolated: a dihydrodiol and two hydroxydihydrodiols were characteristic for the epoxide--diol pathway. There were two dihydroxybiphenyls, a trihydroxybiphenyl, a trihydroxymethoxybiphenyl and 4,4'-dihydroxy-3-methylthiobiphenyl. The mass spectra of the trimethylsilyl derivatives of the metabolites exhibited characteristic doubly charged and metastable ions.

Animals↗
PubMed1978

Methylthio metabolites of naphthalen excreted by the rat.

Eight methylthio metabolites have been found as urinary products of the metabolism of naphthalene in the rat. One was 1-methylthionaphthalene. A second was a methylthio analog and the dihydrodiol, and a third was naphthalene substituted with one hydroxyl and one methylthio group. Two compounds with common structural elements were found; one of these was prepared by synthesis from anti-1,2:3,4-naphthalene dioxide and one from 1 beta, 2 alpha-dithyroxy-3 alpha, 4 alpha-epoxy-1,2,3,4-tetrahydronaphthalene by reaction with 2-keto-4-methylthiobutyric acid or with methionine. Each of these compounds contained one methythio group and three hydroxyl groups substituted on a tetrahydronaphthalene structure. Two metabolites with two methylthio groups and two hydroxyl substituents on a tetrahydronaphthalene ring were also detected; one of these was prepared by synthesis from the dioxide. The most likely metabolic origin of these methylthio metabolites is through the reaction of epoxides (including the diepoxide) with a nucleophile which may be methyl mercaptan, 2-keto-4-methylthiobutyric acid, or methionine.

Animals↗
PubMed1978

Formation in vivo of deuterated methylthio metabolites of naphthalene from L-methionine (methyl-d--3).

Studies were carried out with deuterated methionine (methyl-d--3) to determine if methylthio metabolites of naphthalene were formed in vivo by reaction with methionine-derived metabolites. Rats were maintained on a methionine-free diet for nine days followed by eight days on the same diet supplemented with L-methionine-d--3 prior to administration of naphthalene. When naphthalene metabolites isolated from urine were characterized by GC and GC-MS procedures, it was found that the incorporation of deuterium into the methylthio metabolites, as well as into a catechol methyl ether, was approximately 40%. These results show that the methyl group was derived from methionine.

Animals↗
PubMed1977

Urinary excretion of phenobarbital in a neonate having withdrawal symptoms.

Utilizing methods of gas chromatography-mass spectrometry-computer systems operated in a chemical ionization mode, metabolites of mephobarbital were demostrated in urines collected from two infants whose mother was treated with mephobarbital during pregnancy. Identification of the major metabolite in one infant was possibe for 22 days after delivery. The urinary half-life of mephobartial was 30 hours and the half-life of phenobarbital was 48 hours. Both infants demonstrated withdrawal symptoms for four to six months and manifested the physical phenotype of infants exposed in utero to anticonvulsant agents.

Adult↗
PubMed1977

Use of saliva in therapeutic drug monitoring.

We measured the concentrations of phenobarbital, phenytoin, primidone, ethosuximide, antipyrine, and caffeine in paired samples of saliva and plasma by gas chromatograph-mass spectrometer-computer (GC/MS/COM) and enzyme immunoassay. Mixed saliva was collected for the antipyrine and caffeine studies, parotid saliva for the phenobarbital, primidone, ethosuximide and phenytoin studies. The saliva/plasma (S/P) ratios (by weight) obtained by GC/MS/COM were: phenobarbital, 0.31-0.37; phenytoin, 0.11; ethosuximide, 1.04; antipyrine, 0.83-0.95; caffeine, 0.55. The S/P ratio obtained by enzyme immunoassay were: phenobarbital, 0.32; phenytoin, 0.12; primidone, 0.85. The concentrations of phenytoin, primidone, ethosuximide and antipyrine in saliva correspond to the free fraction of the drug in plasma. When we analyzed samples containing phenobarbital or phenytoin (plasma or saliva) by both techniques, we found that the enzyme immunoassay values were generally higher than GC/MS/COM values, suggesting that the metabolites as well as the parent drug were measured in the immunoassay.

Antipyrine↗
PubMed1976

Profiles of volatile metabolities in body fluids.

A method for the analysis of volatile metabolites present in plasma, urine, breast milk and amniotic fluid collected from mother-infant pairs has been developed which requires only 100 mul of plasma, 3 ml of urine, 20 mul of breast milk and 500 mul of amniotic fluid. After extraction with diethyl ether, the volatile compounds were absorbed on glass wool in a special concentration tube and subsequently desorbed and transferred to a 100-m nickel capillary column for analysis by gas chromatography and gas chromatography-mass spectrometry. The separations, carried out by temperature programming, were complete in 90 min.

Alcohols↗
PubMed1976

Elimination of antipyrine and benzo[a]pyrene metabolism in cultured human lymphocytes.

A strong correlation was found in a carefully selected homogenous population (n = 57) between antipyrine plasma half-life and the percent induction of aryl hydrocarbon hydroxylase by 3-methylcholanthrene in mitogen-stimulated lymphocytes from the same individual. The correlation coefficient of r = 0.923 indicates that antipyrine and benzo[a]pyrene share one or several common determinants that are responsible for the observed interindividual variation in the oxidation rates of the two compounds. When a heterogenous population (n = 80) was studied, the above correlation was not found (r = 0.425).

Adult↗
PubMed1975

The use of gas chromatographic-mass spectrometric-computer systems in pharmacokinetic studies.

Pharmacokinetic studies involving plasma, urine, breast milk, saliva and liver homogenates have been carried out by selective ion detection with a gas chromatographic-mass spectrometric-computer system operated in the chemical ionization mode. Stable isotope labeled drugs were used as internal standards for quantification. The half-lives, the concentration at zero time, the slope (regression coefficient), the maximum velocity of the reaction and the apparent Michaelis constant of the reaction were determined by regression analysis, and also by graphic means.

Chromatography, Gas↗
PubMed1975

An investigation of recurrent pine oil poisoning in an infant by the use of gas chromatographic-mass spectrometric methods.

An 18-month-old infant required six hospital admissions in a period of six months for episodes consisting of coughing, respiratory depression, hematemesis, coma, dehydration, and lesions about the mouth. A negative history of ingestion of toxins was repeatedly obtained from the family and two home inspection by the local Health Department failed to identify potential toxins. Metabolic work-up was entirely negative. Utilizing methods of GC-MS, metabolites of a-terpineol were isolated from infant urine on two admissions to the hospital. These metabolites were confirmed by mass spectrometry to be the same metabolites excreted by Sprague-Dawley rats injected with a-terpineol or pine oil. The child had no additional episodes after physical separation from the home environment.

Animals↗
PubMed1975

Clinical applications of gas chromatograph/mass spectrometer/computer systems.

Gas chromatograph/mass spectrometer/computer systems can be used to quantify a wide variety of compounds of clinical interest. A quadrupole instrument operated in the chemical ionization (Cl) mode was used in these studies. Because of the sensitivity and specificity of selective ion detection, it is possible to make measurements routinely in the nanogram to picogram range, with 0.1-1.0 ml samples of plasma and 1-5 ml samples or urine. Internal standards, preferably stable-isotope-labeled compounds, were added to the biological samples before isolation was begun. We describe clinical applications of these procedures to problems in toxicology, pharmacokinetics, and perinatal pharmacology.

Autoanalysis↗
PubMed1975

Identification and quantification of drugs in human amniotic fluid.

Since drugs administered to gravid females are rapidly transferred to the fetus, transplacentally acquired drugs and drug metabolities should be excreted by the fetus into amniotic fluid. Analyses have been carried out on amniotic fluid obtained at the time of delivery using a gas chromatograph-mass spectrometer-computer system. The drugs that have been identified are caffeine, secobarbital and phenobarbital. Theobromine (3,7-dimethylxanthine) and smaller amounts of 1,7- and 1,3-dimethylxanthine, three metabolites of caffeine, were also found in amniotic fluid, but metabolites of secobarbital and phenobarbital were not detected. It is known that human fetal tissues have active enzyme systems for metabolizing drugs, but these results suggest that this may be a selective rather than general occurence.

Amniotic Fluid↗