GLC-mass spectral determination of mescaline in plasma of rabbits after intravenous injection.

A GLC-mass spectral analysis with a deuterated internal standard was developed to measure plasma mescaline concentrations after intravenous administration to rabbits. The drug and the internal standard were extracted with benzene, derivatized with trifluoroacetic acid anhydride, and chromatographed on 2.5% QF-1 with mass fragmentographic detection. The detection limit is 5 ng/ml of plasma. The relative standard deviation was approximately 5%. The main advantage of this method is that it combines the specificity of the GLC retention time and mass spectral fragmentation pattern with the sensitivity of the mass fragmentographic detection.

Extraction and GLC analysis of pyrithyldione in highly putrified human postmortem samples.

Pyrithyldione was isolated from highly putrified human brain and small intestine samples by ether extraction followed by alumina column cleanup. The total yield was 90+/- 5%. No derivatization was necessary prior to GLC analysis.

The conversion of a standard gas chromatograph to a fused silica capillary system: applications in human toxicology and tropical medicine.

A simple and inexpensive modification of the injection port and detector configuration of a standard gas chromatograph, equipped with a nitrogen-phosphorus detector, permits the installation of a fused silica capillary column. Different ways of connecting the column to the injector and its impact on the interchangeability of the columns are discussed. The application of the system to toxicological determinations of clinical and forensic interest has been investigated, using a direct injection technique. The method allows the quantitative determination of different alkaloids and drugs in human biological samples in the low nanogram range, with reliable reproducibility and linear response.

Paraquat poisoning.

A fatal case of paraquat poisoning is described. Postmortem concentration of paraquat in different tissues reveals that treatment in this case could not prevent lethal tissue accumulation. Although accumulation was more pronounced in renal tissue, lung toxicity caused death. The formation of enormous fecaliths and the appearance of hypercalcemia are reported. Both were most likely connected with Füllers earth therapy. In spite of the fact that the exact nature of the equilibrium between plasma levels and tissue accumulation of paraquat (static or dynamic) is not understood, aggressive treatment must be recommended, even after the distribution phase and despite likely "fatal" plasma levels.

Comparison of a GLC-NPD method with a GLC-MS-SIM procedure for the determination of tilidine and its metabolites in plasma.

A gas liquid chromatographic method with nitrogen-phosphorus detection (GLC-NPD) is compared to a GLC-mass spectrometric determination employing selected ion monitoring (GLC-MS-SIM). These two methods of gas chromatographic separation were shown to be suitable for therapeutic monitoring of tilidine, nortilidine, and bisnortilidine in patients. The pharmacokinetic profile of tilidine was also studied in three normal humans after a single oral dose. Pharmacokinetic parameters such as Cmax, tmax, (t1/2) beta, AUC, AUMC, Vd beta, Cltot, beta, and MRT are derived from model independent pharmacokinetic techniques.

Saliva concentrations of disopyramide cannot substitute the drug's plasma concentrations.

For many drugs the salivary concentration corresponds to the free plasma drug concentration, which may be more closely related to drug activity or toxicity than the total plasma drug concentration. In this study a preliminary investigation was undertaken to determine the feasibility of monitoring saliva levels of disopyramide, an antiarrhythmic drug, for clinical and toxicological purposes. Single oral doses of this compound were administered to healthy volunteers. Stimulated mixed saliva and plasma levels were measured by the EMIT technique. The concentrations of disopyramide in the stimulated mixed saliva tended to be lower than those found in the corresponding plasma sample (fp 0.3-0.5), and the saliva-to-plasma concentration ratio increased with a decreasing salivary pH (pH 6.89, S/P = 0.25; pH 8.15, S/P = 0.08). The correlation between the saliva and the total plasma concentrations was significant but relatively poor, however. Consequently, mixed salivary disopyramide concentrations are a poor indicator of plasma concentrations, even if correction is made for pH change.

Gas chromatographic determination of drug levels for the evaluation of a combined hemoperfusion-hemodialysis treatment.

Recently, the use of a prolonged and combined procedure of hemoperfusion (HP) and hemodialysis (HD) was considered as a treatment for severely intoxicated patients caused by drug overdose. Working in cooperation with different hospitals, this laboratory has been involved with the toxicological analysis of biological samples taken during such a treatment. This paper describes the use of a combined HP/HD treatment, especially the evaluation of the system, by giving the analytical results obtained by gas chromatography. The methods utilized enable this application for routine toxicological analysis.

Disposition of tilidine in a fatal poisoning in man.

A fatal intoxication due to the ingestion of tilidine, a narcotic analgesic, in conjunction with ethanol, is described. Tilidine and its two active metabolites, nortilidine and bisnortilidine, were identified and quantitated in the biological fluids and tissues by thin-layer chromatography (TLC), gas-liquid chromatography with sensitive nitrogen-phosphorus detection (GLC/NPD) and gas-liquid chromatography with mass spectrometric detection (GC/MS). The toxicological results are compared with previously reported 14C-tilidine tissue distributions in rats following oral administration and limited tissue data in a previously reported human fatality. In the present case, the death was attributed to the combined central nervous system-depressing effects of ethanol and tilidine.

A fatal intoxication due to doxepin.

A fatal intoxication due to doxepin, a tricyclic antidepressant, is described. Concentrations of doxepin and its metabolite, desmethyldoxepin, were measured in blood, urine, myocardial, and other tissues using thin layer chromatography (TLC) and gas chromatography equipped with a flame-ionisation detector (GC/FID). The developed technique also permitted the quantitative determination of the cis and trans isomers of doxepin. A very remarkable concentration ratio of doxepin:desmethyldoxepin was observed in myocardial tissues. A detailed report on the possible significance is described.

Application of the combined use of fused silica capillary columns and NPD for the toxicological determination of codeine and ethylmorphine in a human overdose case.

The applicability of capillary gas chromatography to the toxicological analysis of extracts of human tissue samples was investigated for codeine and ethylmorphine in a case of drug overdose. After column extraction, the samples were injected onto a fused silica capillary column, using a direct injection technique. The nitrogen-phosphorus detector provided excellent stability and sensitivity without the need for extensive clean-up procedures.

Combined use of fused silica capillary columns and nitrogen-phosphorus detection for the toxicological analysis of illicit heroin samples.

Capillary GC is applied to the toxicological analysis of illicit heroin samples. The combined use of a permanently deactivated fused silica capillary column, and a nitrogen-phosphorus detector (NPD), allows the separation and determination of nanogram amounts of underivatised opiates, using a direct injection technique.

Suicidal poisoning by MCPA and parathion.

A suicidal poisoning committed by a sixty-five year old woman, who swallowed a bottle of Agroxyl, containing an aqueous 250 g/L solution of the sodium- and potassium salt of 2-methyl-4-chlorophenoxyacetic acid [MCPA], together with lethal amounts of a parathion formulation, is described. The case history, the postmortem examination and the concentrations of parathion and MCPA in the different viscera, are reported in detail. Parathion determination was performed by means of a routine method, previously developed in our laboratory. The MCPA quantification was achieved using a thoroughly evaluated EC- GLC micro-analytical procedure, which is discussed completely. Identity was confirmed by GC-MS. Intake of lethal parathion quantities caused the woman's death with five minutes. This case however is worth reporting, since we had the unique opportunity to establish the early distribution of MCPA through the body, during the short period of survival.

A case of fatal rotenone poisoning in a child.

A case of a fatal rotenone poisoning in a three-and-a-half-year-old girl is described. The case report and autopsy findings are mentioned. For the extraction of rotenone out of biological samples, a solvent partitioning and silica gel open column chromatographic cleanup procedure has been used. The determination of rotenone was performed by high pressure liquid chromatography.

Pharmacokinetic parameters of mescaline in rabbits.

By means of a highly specific and sensitive mass fragmentographic method mescaline was measured in rabbit plasma samples, taken at various points after an i.v. injection. The pharmacokinetic behaviour conformed to the two-compartment open model. Half-life times of alpha and beta phases, velocity constants and steady-state distribution volumes of four subjects are reported.