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Biomedical subjects

R L Foltz

Publications and source records attributed to R L Foltz.

72 records · Page 4Linked to original sources
PubMed1970

Metabolite of (-)-trans-delta 8-tetrahydrocannabinol: identification and synthesis.

The major metabolite of (-)-trans-Delta(8)-tetrahydrocannabinol observed in vivo and formed by hepatic microsomes in vitro is 11-hydroxy-trans-Delta(8)-tetrahydrocannabinol. The metabolite was identified spectroscopically and was synthesized from trans-Delta(8)-tetrahydrocannabinol. In tests with rats, the metabolite produced behavioral effects similar to those imparted by Delta(8)- and Delta(9)-tetrahydrocannabinol.

Animals↗
PubMedDate not supplied

Disposition of intravenous pirmenol.

Twelve patients having frequent premature ventricular complexes (PVCs) averaging more than 60 per hour received a single 150-mg intravenous dose of pirmenol. Plasma pirmenol concentration declined biexponentially following the infusion and was analyzed according to a two-compartment open model. Following an erratic distribution phase, the terminal elimination half-life ranged from 4.2 to 16.9 hours, with a geometric mean of 7.6 hours. Total body clearance averaged 164 +/- 58 ml/min, and the mean volume of distribution was 1.45 +/- 0.38 liter/kg. Renal clearance averaged 46.6 +/- 21.2 ml/min, representing 30 +/- 10 per cent of total body clearance. Excretion of unchanged drug in the urine averaged 31.8 +/- 8 per cent of the dose. Renal clearance and elimination half-life were correlated (r = -0.61, P less than 0.05). Eight of the 12 patients achieved greater than 95 per cent suppression of PVCs with a duration between 20 minutes and 23 hours. These favorable pharmacokinetics indicate that pirmenol may be a useful addition to the therapy of ventricular arrhythmias.

Adult↗
PubMedDate not supplied

In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector.

Four biotransformation pathways of 3,4-(methylenedioxy)methamphetamine (MDMA) in the rat have been identified: N-demethylation, O-dealkylation, deamination, and conjugation (O-methylation, O-glucuronidation, and/or O-sulfation). The specific MDMA metabolites that have been identified are 3-hydroxy-4-methoxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxyamphetamine, 3,4-(methylenedioxy)amphetamine (MDA), (4-hydroxy-3-methoxyphenyl)acetone, [3,4-(methylenedioxy)phenyl]acetone, and (3,4-dihydroxyphenyl)acetone. All except 3,4-dihydroxymethamphetamine were present in the urine. The hydroxylated metabolites were excreted in the urine as the O-glucuronide and/or O-sulfate conjugates, but traces of free 4-hydroxy-3-methoxymethamphetamine and 4-hydroxy-3-methoxyamphetamine were also present in unhydrolyzed urine. N-Demethyl and 3-O-methyl phenolic amine metabolites of MDMA were consistently present in brain, liver, blood, and feces. MDMA was metabolized by the 10000g rat liver supernatant to 4-hydroxy-3-methoxymethamphetamine, 3,4-dihydroxymethamphetamine, MDA, and [3,4-(methylenedioxy)phenyl]acetone. Also, the 10000g rat brain supernatant metabolized MDMA to 4-hydroxy-3-methoxymethamphetamine, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxyamphetamine, and MDA.

3,4-Methylenedioxyamphetamine↗
PubMedDate not supplied

Determination of LSD in urine by capillary column gas chromatography and electron impact mass spectrometry.

A procedure for the determination of LSD (lysergic acid diethylamide) in urine at concentrations as low as 0.5 ng/ml is presented. After addition of deuterium-labeled LSD as the internal standard, a rapid n-butyl chloride extraction of LSD from urine at pH 8 is followed by formation of the trimethylsilyl (TMS) derivative by treatment with N,O-bis(trimethylsilyl)trifluoroacetamide. The TMS derivative of LSD is identified and quantified by selected ion monitoring with a fused-silica capillary column and electron impact ionization. The procedure was used to monitor LSD concentrations in urine for eight hours following oral administration of 70.5 micrograms of LSD to two human volunteers. Concentrations of LSD determined by the assay are compared with concentrations determined by two other methods of analysis, a radioimmunoassay and a high-performance liquid chromatographic (HPLC) assay. Data concerning the stability of LSD in urine are also presented.

Chromatography, Gas↗
PubMedDate not supplied

Measurement of lysergic acid diethylamide (LSD) in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry.

A previously reported procedure for quantification of LSD in urine was modified to permit measurement of the drug in plasma. After addition of deuterium-labelled LSD, the plasma is extracted and the extract is treated with trifluoroacetylimidazole to convert the LSD to its N-trifluoroacetyl derivative. The derivatized LSD is analyzed by capillary column gas chromatography/negative ion chemical ionization. Plasma fortified with known concentrations of LSD gave linear responses from 0.1 to 3.0 ng/mL with this assay. The method was used to determine pharmacokinetic parameters for LSD after oral administration (1 microgram/kg) to a male volunteer. The apparent plasma half-life was determined to be 5.1 h. The peak plasma concentration of 1.9 ng/mL occurred 3 h after administration.

Administration, Oral↗
PubMedDate not supplied

Cocaine metabolism in man: identification of four previously unreported cocaine metabolites in human urine.

Cocaine and 11 of its metabolites were identified in a urine specimen from a cocaine user. Four of the metabolites are reported for the first time: ecgonidine, norecgonidine methyl ester, norecgonine methyl ester, and m-hydroxy-benzoylecgonine. The structures of the newly identified metabolites were confirmed by comparison of their gas chromatographic retention times and their electron ionization and chemical ionization mass spectra with the corresponding data obtained on synthesized standards. Other metabolites present were benzoylecgonine, ecgonine methyl ester, ecgonine, ecgonidine methyl ester, norcocaine, p-hydroxycocaine, and m-hydroxycocaine.

Cocaine↗
PubMedDate not supplied

Comparison of a TLC method with EMIT and GC/MS for detection of cannabinoids in urine.

Urine specimens were analyzed in parallel with a new TLC method, an EMIT assay, and a reference GC/MS method. At a 9-carboxy-THC cutoff of 20 ng/mL, the TLC method correctly identified 92% of the positive urines and 97% of the negative urines. In contrast, only 63% of the urine specimens shown by GC/MS to contain greater than 20 ng/mL of 9-carboxy-THC were identified as positive by the EMIT d.a.u. assay at the 100-ng/mL cannabinoid cutoff.

Cannabinoids↗
PubMedDate not supplied

Analysis of naltrexone and 6-beta-naltrexol in plasma and urine by gas chromatography/negative ion chemical ionization mass spectrometry.

A procedure for the analysis of naltrexone and 6-beta-naltrexol in plasma and urine samples is described. The method takes advantage of the specificity of negative ion chemical ionization mass spectrometry and the resolving power of capillary column chromatography to achieve a limit of quantitation of 0.1 ng/mL. The trideuterated analogs of naltrexone and 6-beta-naltrexol are used as internal standards. Samples are first made basic with K2HPO4 buffer (50% w/v), and then extracted twice with n-butyl chloride-acetonitrile (4:1). After back extraction into 0.2 N H2SO4, the samples are again extracted with n-butyl chloride-acetonitrile. The extracts are derivatized with 2% methoxyamine in pyridine and pentafluoropropionic anhydride to form the methoxime bis-(pentafluoropropionyl) derivative of naltrexone and the tris-(pentafluoropropionyl) derivative of 6-beta-naltrexol. The derivatized extracts are analyzed by selected ion monitoring of prominent ions formed by electron-capture negative ion chemical ionization.

Delayed-Action Preparations↗
PubMedDate not supplied

Determination of naltrexone and 6-beta-naltrexol in plasma by solid-phase extraction and gas chromatography-negative ion chemical ionization-mass spectrometry.

Solid-phase extraction (SPE) and a one-step derivatization are combined with gas chromatography-negative ion chemical ionization-mass spectrometry to simplify a previously reported method for the determination of naltrexone and its metabolite, 6-beta-naltrexol, in human plasma. Deuterated isotopomers of naltrexone and 6-beta-naltrexol are used as internal standards. After SPE, the extracts are derivatized with pentafluoropropionic anhydride at room temperature to form predominantly the bispentafluoropropionyl derivative of naltrexone and the trispentafluoropropionyl derivative of 6-beta-naltrexol. The derivatized extracts are analyzed by monitoring ion currents at m/z 633 (naltrexone), m/z 636 (naltrexone-2H3), m/z 633 6-beta-naltrexol), and m/z 640 (6-beta-naltrexol-2H7). Control plasma samples containing 0.3, 3, or 30 ng/nl of each analyte were analyzed for precision and accuracy with the following results: intra-assay, the percentage of target concentrations were 107-113% for naltrexone and 107-120% for 6-beta-naltrexol, and the coefficients of variation (CVs) were 3.1-6.3% for naltrexone and 3.1-5.7% for 6-beta-naltrexol; interassay, the percentage of target concentrations were 103-110% for naltrexone and 110-113% for 6-beta-naltrexol, and the CVs were 6.1-9.1% for naltrexone and 5.9-9.1% for 6-beta-naltrexol. At the limit of quantitation (LOQ) of 0.1 ng/ml, both analytes quantified within 20% of the target concentration with CVs less than 17%. The extraction recoveries determined at 0.3 and 30 ng/ml were 79 and 80% for naltrexone and 76 and 75% for 6-beta-naltrexol. Bench-top stability tested with concentrations of 0.3 and 3.0 ng/ml did not decrease more than 10% from the zero-hour controls at 3, 6 and 24 h. Selectively was determined using plasma from six donors and none showed interfering peaks greater than 22% of the LOQ for naltrexone and 53% of the LOQ for 6-beta-naltrexol. Using this method, naltrexone and 6-beta-naltrexol were readily detected in plasma specimens collected 5.5 h after oral doses of 25 or 100 mg naltrexone. Following discontinuation of treatment, naltrexone was detected 30 h after the 100-mg dose, whereas 6-beta-naltrexol was detected 125 h after both the 25- and 100-mg doses.

Drug Stability↗
PubMedDate not supplied

Cannabinoid concentrations in plasma after passive inhalation of marijuana smoke.

delta-9-tetrahydrocannabinol (THC) and its metabolite, 9-carboxy-THC, were detected in the plasma of a subject during a one-hour passive exposure to the smoke from four marijuana cigarettes containing a total of 104.8 mg of THC. Plasma concentrations of THC were determined by RIA and reached an apparent steady-state concentration of 2.2 ng/mL after 20 minutes of exposure. The presence of THC was confirmed by GC/MS analysis. Results from the two analyses exhibited excellent correlation (r = 0.990), although the concentrations determined by GC/MS were higher than those determined by RIA. Concentrations of 9-carboxy-THC were also determined by GC/MS, and remained consistently below the GC/MS determined concentrations of THC. By administering an infusion of THC, the dose that was inhaled and absorbed during the passive exposure was estimated to be 3.2 micrograms/min.

Adult↗
PubMedDate not supplied

Evaluation of immunoassays for cannabinoids in urine.

A comparison was made of several cannabinoid urine assays. Two hundred randomly selected urine specimens were initially screened by two enzyme immunoassays (EMIT-st and EMIT-d.a.u.) and a radioimmunoassay (Abuscreen RIA). Selected specimens found positive by any of these methods were further analyzed by gas-liquid chromatography with flame ionization detection (GLC/FID), gas chromatography/mass spectrometry (GC/MS), and an experimental RIA from Research Triangle Institute (RTI RIA). The GLC/FID method gave confirmations in 69 to 92% of the samples, depending on the method used and the cut-off employed. GC/MS confirmed 98% of the EMIT and RIA positives using a low cut-off (20 ng/mL). All RIA positives at 100 ng/mL were confirmed by GC/MS. There was complete agreement between the RTI RIA and the EMIT assays, but not with the Abuscreen RIA at the 100 ng/mL cut-off. The study illustrates that care must be exercised in establishing assay cut-offs and the designation of false positive results.

Cannabinoids↗
PubMedDate not supplied

Stability of delta 9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC in blood and plasma.

The stabilities of delta 9-tetrahydrocannabinol (THC) and two of its metabolites, 11-hydroxy-delta 9-tetrahydrocannabinol (HO-THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (COOH-THC), were determined in blood and plasma stored at -10 degrees C, 4 degrees C, and room temperature. Each of the cannabinoids was added to freshly-drawn blood and plasma to give concentrations of 20 ng/mL. Two-mL aliquots were stored in silanized tubes and the cannabinoid concentrations were monitored by gas chromatography/mass spectrometry over a 6-month period. No significant changes were observed in the concentrations of the cannabinoids for the first month of storage. However, the concentrations of THC and HO-THC in blood stored at room temperature had decreased significantly at 2 months. No statistically significant changes were detected in cannabinoid concentrations in plasma or blood stored at 4 degrees or -10 degrees C for up to 4 months. After 6 months at room temperature, the blood concentrations of THC and HO-THC had decreased by 90 and 44%, respectively, whereas the concentration of COOH-THC was not significantly different from the control. The possibility of loss of cannabinoids from blood due to adsorption onto the grey stoppers used in Venoject tubes was also investigated. Over a 24-hr period, no significant differences were detected in any of the cannabinoid concentrations regardless of sample size (1.3 or 8 mL), differences in temperature (-10 degrees C, 4 degrees C, or room temperature), or extent of contact with the tube's stoppers.

Dronabinol↗