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R L Foltz

Publications and source records attributed to R L Foltz.

At least 55 records · Page 3Linked to original sources

Quantitative measurement of delta 9-tetrahydrocannabinol and two major metabolites in physiological specimens using capillary column gas chromatography negative ion chemical ionization mass spectrometry.

delta 9-Tetrahydrocannabinol and two of its metabolites, 11-hydroxy-delta 9-tetrahydrocannabinol and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol, can be measured in a single 1-ml sample of blood, plasma, or urine by a new assay which combines a relatively rapid extraction procedure with capillary column gas chromatography and negative ion chemical ionization mass spectrometry. Deuterium-labeled analogs of each cannabinoid are added to the physiological specimen as internal standards. Two extracts are obtained from each sample: a neutral fraction containing delta 9-tetrahydrocannabinol and 11-hydroxy-delta 9-tetrahydrocannabinol, and an acid fraction containing 11-nor-9-carboxy-delta 9-tetrahydrocannabinol. The neutral fraction is derivatized by treatment with trifluoroacetic anhydride; the acid fraction is first treated with BF3-methanol followed by reaction with trifluoroacetic anhydride. Under electron-capture chemical ionization conditions the derivatized delta 9-tetrahydrocannabinol and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol give abundant molecular anions ideally suited for selected ion monitoring. The negative ion chemical ionization spectrum of the HO-THC-trifluoroacetate shows no molecular anion. Consequently, quantitation of the hydroxy metabolite is achieved by monitoring a fragment ion formed by loss of CF3CO2 from its molecular anion. The limits of reliable measurement are judged to be 0.1 ng ml-1 for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol, 0.2 ng ml-1 for delta 9-tetrahydrocannabinol and 0.5 ng ml-1 for 11-hydroxy-delta 9-tetrahydrocannabinol. Four examples are given of the application of the assay to the analysis of specimens of medico-legal importance.

Adult↗

Quantitative analysis for delta 9-THC, 11-hydroxy-delta 9-THC, and 9-carboxy-delta 9-THC in plasma using GC/CI-MS.

A method for quantitative measurement of delta 9-THC concentrations in plasma has been developed and applied to the analysis of more than 2000 samples over the past 4 years. The method includes addition of deuterium-labeled delta 9-THC to the plasma for use as the internal standard, a simple and relatively rapid solvent extraction procedure, formation of the trimethylsilyl derivative, and quantitation by selected ion monitoring using ammonia chemical ionization. A similar procedure has also been developed for simultaneous analysis of delta 9-THC and two of its major metabolites in plasma. The latter procedure requires use of a glass capillary column for assays of plasma samples in which the delta 9-THC concentration is below 10 ng/ml. Sensitivities for both methods permit quantitation of THC and its metabolites at concentrations as low as 0.2 ng in 1-ml plasma samples.

Dronabinol↗

Meperidine and normeperidine levels following meperidine administration during labor. I. Mother.

Because of the unavailability of sensitive analytic techniques, the pharmacokinetics of meperidine have not been clearly delineated in obstetric patients during labor. Moreover, the production of the active meperidine metabolite--normeperidine--has not been investigated. By means of gas chromatographic and mass spectrometric techniques, these characteristics of meperidine metabolism were evaluated in 23 pregnant patients in the present study. The data show that the disappearance curve and pharmacokinetic constants for meperidine are similar to those previously reported for nonpregnant subjects. In regard to normeperidine, the data indicate that it is produced within ten minutes after meperidine injection, increases rapidly for the next 20 minutes, and then slowly increases throughout labor. The results enumerate the pharmacokinetic constants of meperidine in obstetric patients and describe the appearance of normeperidine, the active meperidine metabolite, following meperidine administration during labor.

Adult↗

Ring formation in a pentapeptide with alternating L and D residues: an analogy to cyclization in the biosynthesis of peptide antibiotics.

Acetylation of L-isoleucyl-D-alanyl-D-alanyl-L-valyl-D-leucine with acetic anhydride followed by methylation with diazomethane yielded the expected acetylpentapeptide methyl ester with molecular weight 541, but also resulted in the formation of a by-product with molecular weight 555. The incorporation of the mass corresponding to CH2 seems to be due to ring closure--via a mixed anhydride--and methylation of the cyclol derivative thus formed. A preferred, ring-like conformation stabilized by intramolecular hydrogen bonds that in turn are the consequences of the alternation of D- and L- residues in the sequence, is invoked as explanation for the unexpected cyclization. This assumption is supported by the conversion of the pentapeptide methyl ester to desthiomalformain in molten imidazole.

Acetylation↗

Analysis of benzoylecgonine in urine by high-performance liquid chromatography and gas chromatography-mass spectrometry.

Benzoylecgonine, a polar metabolite of cocaine, was extracted and purified from urine using a reversed-phase high-performance liquid chromatographic column. The portion of the eluent corresponding to elution of the drug was collected, derivatized, and quantified using gas chromatography-mass spectrometry with selected ion monitoring. Using this procedure, analysis of 1 ng/ml of benzoylecgonine in urine can be achieved.

Chromatography, Gas↗

Long-retained metabolites of delta9- and delta8-tetrahydrocannabinols identified as novel fatty acid conjugates.

Long-retained metabolites of delta9-tetrahydrocannabinol (delta9-THC) and delta8-tetrahydrocannabinol (delta8-THC) previously detected in the liver, spleen, fat, and bone marrow of the rat after I.V. or I.P. injections of 14C-delta8-THC or 14C-delta9-THC, have been identified as fatty acid conjugates of 11-hydroxy-delta9-THC and 11-hydroxy-delta8-THC. Characterization of the metabolites was facilitated by their large-scale in vitro production from 11-hydroxy-delta9-THC and 11-hydroxy-delta8-THC with a rat-liver microsomal enzyme system. Conjugation of long-chain fatty acids to drugs or their hydroxylated metabolites may have considerable biological significance.

Animals↗

Chemical-ionization mass spectrometry of beta-lactam antibiotics.

Chemical-ionization (CI) mass spectra are described for methyl esters of eight clinically significant penicillins and their breakdown products. The substances give spectra with very few fragment ions and contain easily discernible protonated molecule ions. The main cleavage reaction is postulated to involve a retro 2+2 Diels-Alder-type fragmentation of the beta-lactam ring liberating one fragment (m/e=174) that is characteristic of the penicillin nucleus and a second fragment that is molecule specific, as it contains the elements of the side chain. The other fragment ions, though interesting, are of minor intensity. The free acids, on the other hand, fragment more extensively because of their relative instability and lack of volatility. These spectra resemble electron impact spectra more closely and, though they encode more structural information, are less reproducible from run to run. The ease with which the esters can be made and the relative simplicity of their CI mass spectra make this method significant for the identification and characterization of beta-lactam antibiotics.

Esters↗