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Biomedical subjects

D L Hachey

Publications and source records attributed to D L Hachey.

64 records · Page 4Linked to original sources
PubMed1982

Quantitation of methadone enantiomers in humans using stable isotope-labeled [2H3]-, [2H5]-, and [2H8]Methadone.

A new technique for simultaneous stereoselective kinetic studies of methadone enantiomers was developed using three deuterium-labeled forms of methadone and GLC-chemical-ionization mass spectrometry. A racemic mixture (1:1) of (R)-(-)-[2H5]methadone (l-form) and (S)-(R)-[2H3]methadone (d-form) was administered orally in place of a single daily dose of unlabeled (+/-)-[2H0]methadone in long-term maintenance patients. Racemic (+/-)-[2H8]methadone was used as an internal standard for the simultaneous quantitation of [2H0]-, [2H3]-, and [2H5]methadone in plasma and urine. A newly developed extraction procedure, using a short, disposable C18 reversed-phase cartridge and improved chemical-ionization procedures employing ammonia gas, resulted in significant reduction of the background impurities contributing to the ions used for isotopic abundance measurements. These improvements enabled the measurement of labeled plasma methadone levels for 120 hr following a single dose. This methodology was applied to the study of methadone kinetics in two patients; in both patients, the analgesically active l-enantiomer of the drug had a longer plasma elimination half-life and a smaller area under the plasma disappearance curve than did the inactive d-form.

Adult↗
PubMed1977

Quantitative analysis of methadone in biological fluids using deuterium-labeled methadone and GLC-chemical-ionization mass spectrometry.

The (+)-,(-)-, and (+/-)-2H5-methadones, which contained five deuterium atoms in one aromatic ring, were synthesized for use in clinical pharmacological studies and as internal standards. GLC-chemical-ionization mass spectrometry was used to determine plasma and urinary methadone levels by an inverse isotope dilution assay. Plasma drug levels could be determined to 10 pmoles/ml, and urine levels could be measured to 5 pmoles/ml. Plasma methadone levels were examined in several patients undergoing methadone maintenance therapy. These levels generally ranged between 100 and 400 ng/ml (320-1300 pmoles/ml) after an average oral dose of 1 mg/kg/day. The methadone half-life was 28.8 +/- 4.8 hr.

Adult↗
PubMed1977

An improved procedure for the synthesis of glycine and taurine conjugates of bile acids.

Glycine and taurine conjugates of 5beta-cholanic acids have been synthesized using improved procedures based on the peptide coupling reagent, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. The conjugates are obtained in chromatographically pure form in yields higher than 90%. The use of this procedure in the large scale preparation of cholyl[1,2-13C2]glycine is described.

Bile Acids and Salts↗
PubMed1976

Synthesis of 11, 12-2H2- and 11, 12-3H2-labeled chenodeoxycholic and lithocholic acids.

Deuterium- and tritium-labeled chenodeoxycholic acid and lithocholic were prepared by catalytic reduction of their respective delta11 derivatives. Structures of the intermediates and their isotopic purity were verified by chemical ionization and electron impact mass spectrometry and by nuclear magnetic resonance spectroscopy. Experimental conditions for reductive deuteration were defined which gave complete reduction of the olefin and a product of high isotopic purity. Conditions for optimal tritiation were developed with which little exchange of protons with the solvent occurred; the product had high specific activity. To test biological stability of the label, the 3H-labeled chenodeoxycholic acid was administered simultaneously with 14C-labeled chenodeoxycholic acid to two healthy subjects and the 3H/14C ratio in bile was determined daily for several days. The ratio remained identical to that administered, suggesting that the 11,12-3Hlabel in chenodeoxycholic acid is stable during enterohepatic cycling and can be used for valid estimates fo bile acid kinetics in many by the isotope dilution technique.

Chenodeoxycholic Acid↗
PubMed1976

Characterization of bile acid methyl ester acetate derivatives using gas-liquid chromatography, electron impact, and chemical ionization mass spectrometry.

The gas-liquid chromatographic retention times on 0.5% SP-525 for 48 bile acids and related compounds as their methyl ester acetate derivatives are given. Ion tables for electron impact spectra have been compiled that permit direct access to ion structures for any given ion mass. Chemical ionization yields highly simplified mass spectra with two or three ions predominating for each compound. When the relative retention times of bile acids as their methyl ester acetates are combined with selective ion monitoring techniques in chemical ionization mass spectrometry, the retention time and ion mass number form a coordinate system which can be a powerful tool in the characterization of bile acid mixtures.

Acetates↗
PubMed1975

Stable isotope ratiometer-multiple ion detector unit for quantitative and qualitative stable isotope studies by gas chromatography-mass spectrometry.

We have designed and constructed a stable isotope ratiometer-multiple ion detector unit, which can drive existing chromatograph-quadrupole or magnetic sector mass gas spectrometers to monitor up to six ions in turn. Each of the three pairs of ions can be selected for quantitation; thus three different or successive components can be analyzed in a single gas-chromatographic run. A background subtraction option permits the ion intensity in the absence of sample to be subtracted automatically during sample measurement. Displays of accumulated counts and isotope ratio are updated twice per second during the measurement and can be printed out at is conclusion. All six ions can be monitored in the analog mode by parallel outputs to a multipen recorder. Experience gained in the construction of this prototype indicates that such units could be commercially available for $10 000, or about a third to a sixth of the cost of even an inexpensive computer system.

Autoanalysis↗