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.

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 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.

In vitro adsorption of tilidine HCl by activated charcoal.

In vitro studies were carried out in order to determine the adsorption of tilidine HCl, a narcotic analgesic, by activated charcoal (max. adsorption capacity 185.5 mg/g of charcoal). The path of the adsorption isotherms at pH 1.2 and 7.5 suggests that the in vivo adsorption of tilidine HCl may be increased when the drug passes from the stomach to the intestine, unless the intestinal content exerts a displacing effect. Nevertheless, the adsorption was dependent on the quantity of activated charcoal used, becoming more complete when the quantity of activated charcoal was increased. The effects of additives on the adsorption capacity of activated charcoal were also investigated in vitro. Ethanol, sorbitol and sucrose significantly reduced drug adsorption, while cacao powder, milk and starch had no effect on tilidine adsorption. At an acid pH, Federa Activated Charcoal significantly adsorbed more drug than either Norit A or Activated Charcoal Merck.

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.

Hair copper in intrauterine copper device users.

The antifertility effect of copper-bearing IUDs is based on continuous release of copper, which is a result of the reaction between the metal and the uterine secretions. Released cupric ions collect in the endometrium and in the uterine fluid but significant accumulation has not been found in the bloodstream or elsewhere. Following Laker's suggestion that hair be used for monitoring essential trace elements, e.g., copper, we checked the copper content of the hair of women wearing copper-bearing IUDs. Samples of untreated pubic hair removed by clipping before diagnostic curettage were obtained from 10 young (24-34 years old), white caucasian females who until then had been wearing an MLCu250 IUD for more than 1 year. Pubes from 10 comparable (sex, age, race) subjects who had never used a Cu-containing device served as controls. The unwashed material was submitted to the toxicology laboratory, where the copper content was assessed by flameless atomic absorption, a technique whose lower limit of measurement lies at a concentration of 0.05 mcg Cu/ml fluid (50 ppb). Hair samples were washed to remove extraneous traces of metal according to the prescriptions of the International Atomic Energy Agency, weighed, and mineralized, after which a small volume (10 mcl) of the diluted fluid was fed into the graphite furnace. Each sample (75-150 mg) was analyzed 4 times, both before and after washing. Since the cleaning procedure reduces the weight of the sample (mainly by the removal of fat, dust, etc.) this explains why the percentage copper content of washed hair is higher than that of unwashed hair belonging to the same subject. The results indicate that there was no significant difference (Mann-Whitney U test) between the mean copper levels of both unwashed and washed pubes from women who were using or had never used an MLCu250 IUD. We therefore conclude that the use of this copper-containing device is not associated with significant accumulation of copper in (pubic) hair.

Determination by flameless atomic absorption of aluminium in serum and hair for toxicological monitoring of patients on chronic intermittent haemodialysis.

Determination of aluminium in serum of patients on chronic intermittent haemodialysis is of paramount importance in the prevention or early diagnosis of aluminium intoxication. We present a new method based on flameless atomic absorption spectroscopy, in which the serum matrix is destroyed by oxygen. A comparison has been made between the described method and another procedure which is used in the Laboratory of Toxicology in Ghent, with favourable results. In addition, a method is presented for the determination of aluminium in hair, in which special attention has been paid to the cleaning of the hair samples prior to destruction. As yet it cannot be concluded whether aluminium concentrations in hair give a better representation of the body burden than serum levels do.