D.D. Breimer

Gas chromatographic determination of chloral hydrate, trichloroethanol and trichloroacetic acid in blood and in urine employing head-space analysis

Abstract A specific and sensitive gas chromatographic method for the quantitative determination of chloral hydrate and its metabolites trichloroethanol, trichloroethanol glucuronide and trichloroacetic acid in blood and urine is described. Use is made of the relative volatility of trichloroacetaldehyde, trichloroethanol and trichloroacetic acid methyl ester, which offers the possibility of head-space analysis. A known volume of the head-space gas, in equilibrium with its liquid phase (blood or urine), is directly injected into the gas chromatograph, which is equipped with an electron capture detector. Samples are divided in two portions: 1.0 ml for the determination of unconjugated trichloroethanol and 2.0 ml+1.0 ml of concentrated sulphuric acid for the determination of chloral hydrate, trichloroethanol (conjugated+unconjugated) and trichloroacetic acid after esterification with dimethyl sulphate. Detection limits for chloral hydrate and trichloroethanol are 0.5 μg/ml in blood or urine and for trichloroacetic acid 0.1 μg/ml. Some preliminary pharmacokinetic studies on chloral hydrate and its metabolites in dogs and humans are reported.

Rapid and sensitive gas chromatographic determination of hexobarbital in plasma of man using a nitrogen detector

Abstract The use of a nitrogen detector (alkali flame ionization detector) in a gas chromatographic method for the assay of hexobarbital in plasma is described. After extraction of the samples with light petroleum (boiling range 40–60°)-amyl alcohol (100:2), using methohexital as the internal standard, direct analysis is carried out. The high sensitivity and selectivity of the nitrogen detector permit the determination of hexobarbital in plasma at levels down to 50 ng/ml. The sensitivity and selectivity are compared with those obtained in normal flame ionization detection. A procedure is given for the purification of plasma samples of hepatitis patients with a high bilirubin content. Some pharmacokinetic applications of the method are reported.

Pharmacokinetics of hexobarbital in man after intravenous infusion

The plasma levels of hexobarbital in humans were determined during and after a 30-min or 60-min zero-order intravenous infusion. Hexobarbital kinetics could be described by conceiving the body to exhibit two compartments. The plasma concentrations were fitted to the postinfusion equation and the parameters intrinsic to the two- compartment open model were estimated. The elimination half-life varied considerably among the 14 individuals (160–441 min), which could mainly be explained by the greatly varying metabolic clearance of the compound (123–360 ml /min). The apparent volume of distribution per kilogram of body weight was relatively constant (1.10±0.12 liters/kg).

Identification of cannabivarins in hashish by a new method of combined gas chromatography-mass-spectrometry

Abstract The cannabis constituents cannabidiol, tetrahydrocannabinol and cannabinol in hashish are accompanied by the propyl analogues cannabidivarin, tetrahydrocannabivarin and cannabivarin. A new method was developed to identify these compounds by means of the combined gas chromatograph-mass spectrometer.

Gas chromatography of cannabis constituents and their synthetic derivatives

Abstract Twenty-five natural and forty-five synthetic cannabinoids have been identified by gas chromatography-mass spectrometry. It appeared that the retention times of groups of cannabinoids showed a characteristic pattern. An increase in the side-chain increases the retention time by a fixed amount of 42% per carbon atom. When the position of the side-chain is shifted from the ortho to the para position of the aromatic ring, the retention time is increased by a factor of 1.3. Reduction of the polarity by methylation and silylation reduces the retention time by a factor of 0.53. Branching of the side-chain results in an increase in the retention time by 12%. Saturation of the double bonds leads to a decrease in the retention time by a factor of 0.80.

Pharmacokinetics of the enantiomers of hexobarbital studied in the same intact rat and in the same isolated perfused rat liver.

Abstract The pharmacokinetics of (+)- and (−)-hexobarbital were studied in the same intact rat after i.v. administration, as well as in the same isolated rat liver. The blood half-life of (+)-hexobarbital was 2–3 times shorter than than of (−)-hexobarbital, both in vivo and in vitro. No differences in apparent volume of distribution were observed, but the metabolic clearance of (+)-hexobarbital was 2–3 times greater. Clearance values in vivo were found to be equal to those in vitro for the same compound. No differences in binding to 3% albumin were observed at 3 physiological concentrations, determined by equilibrium dialysis. The animals slept much longer after injection of (+)-hexobarbital and the blood concentration at the moment of awakening was approximately 4 times lower than after injection of (−)-hexobarbital. It is suggested that a difference in anesthetic potency between the hexobarbital enantiomers at the CNS level is likely to exist.

Gas chromatography of cannabinoids. Gas chromatographic behaviour of cis- and trans- tetrahydrocannabinol and isotetrahydrocannabinol.

Abstract Synthetic side-products of tetrahydrocannabinols (1,6-, 1,2- and iso-THC) were submitted to gas chromatographic—mass spectrometric analysis and the compounds were identified by mass spectrometry. The gas chromatographic behaviour of the THC isomers is very characteristic and there are fixed ratios of the retention times for the cis-trans -isomers (1.85), ortho/para -isomers (1.20) and iso-THC/1,2-THC (2.67 and 4.80).

Cannabivarichromene, a new cannabinoid with a propyl side chain in cannabis

Es wurde ein neuer Vertreter aus der Gruppe der psychotrop wirkenden Inhaltsstoffe im Haschisch indischer Herkunft gefunden. Es handelt sich um Cannabivarichromen, als Homologa mit einer Propyl-Seitenkette des Cannabichromens.