Screening for and validated quantification of phenethylamine-type designer drugs and mescaline in human blood plasma by gas chromatography/mass spectrometry.

In recent years, several newer designer drugs of the so-called 2C series such as 2C-D, 2C-E, 2C-P, 2C-B, 2C-I, 2C-T-2, and 2C-T-7 have entered the illicit drug market as recreational drugs. Some fatal intoxications involving 2C-T-7 have been reported. Only scarce data have been published about analyses of these substances in human blood and/or plasma. This paper describes a method for screening and simultaneous quantification of the above-mentioned compounds and their analog mescaline in human blood plasma. The analytes were analyzed by gas chromatography/mass spectrometry in the selected-ion monitoring mode, after mixed-mode solid-phase extraction (HCX) and derivatization with heptafluorobutyric anhydride. The method was fully validated according to international guidelines. Validation data for 2C-T-2 and 2C-T-7 were unacceptable. For all other analytes, the method was linear from 5 to 500 microg/L and the data for accuracy (bias) and precision (coefficient of variation) were within the acceptance limits of +/-15% and <15%, respectively (within +/-20% and <20% near the limit of quantification of 5 microg/L).

A mescaline associated fatality.

The death of an individual under the influence of mescaline is presented. Concentrations of the drug were 9.7, 70.8, and 1163 micrograms/mL or micrograms/g in blood, liver, and urine respectively.

Effect of clozapine and molindone on plasma and brain levels of mescaline in mice.

Levels of unchanged mescaline were examined in the plasma and brain of albino Swiss-Webster mice pretreated with various doses of either clozapine or molindone. In clozapine treated mice, the mescaline levels were statistically significantly higher at 2 and 3 h with 7.5 and 15.0 mg/kg and at 1, 2 and 3 h with 30 mg/kg. Molindone at 4.0 and 8.0 mg/kg produced no significant effect; at 16.0 and 48.0 mg/kg, the levels were significantly higher at 1 and 2 h. Elevated brain levels of mescaline by clozapine and molindone indicate an adverse metabolic interaction between a hallucinogen and drugs that are commonly used to treat mescaline-induced psychosis.

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.

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.

Disposition of 14C-mescaline by rabbit lung.

Metabolism of mescaline by several rabbit tissues was examined in vitro. Mescaline-oxidizing activity (micromoles per milligram of protein/15 min) of lung homogenates was 4 times greater than that of either liver or kidney. Brain and plasma each had comparatively little capacity to metabolize mescaline. Mescaline metabolism in vitro was sensitive to inhibition by semicarbazide. Removal of mescaline from the medium perfusing the isolated rabbit lung was explained by intrapulmonary metabolism. Semicarbazide (10(-3) M pargyline. Semicarbazide-treated lungs accumulated more mescaline than did untreated lungs. Mescaline efflux from lung was slower than that of its metabolite. These results indicate that the intact lung removes perfused mescaline and may be important in the disposition of circulating mescaline in vivo.