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We report two fatalities involving the new designer drug methedrone, 4-methoxymethylcathinone. Blood was extracted with ethyl acetate after the addition of sodium hydroxide followed by evaporation and derivatization with TFAA before gas chromatography-mass spectrometry analysis. Hair was decontaminated and cut into segments, and after overnight extraction with acetonitrile/methanol/20 mM ammonium formate buffer (pH 3) (10:10:80), samples were analyzed by liquid chromatography-tandem mass spectrometry. The first case was treated in hospital, and blood was collected for drug screening. The concentration of methedrone in antemortem blood was 13.2 μg/g and in postmortem femoral blood 8.4 μg/g. The second case presented with 9.6 μg methedrone/g femoral blood, and in a hair sample, methedrone was detected in five short segments suggesting exposure to the drug during the months prior to death. In living abusers, the blood concentration range was 0.2-4.8 μg/g (n = 11). We conclude that use of methedrone may result in accidental death owing to its toxic properties and that the blood concentrations found in the two cases are close to those seen in the living. This suggests a rather narrow "therapeutic" window and emphasizes the danger in taking this kind of drug for recreational purposes.

The aim of this study was to develop a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the analysis of benzodiazepines in human hair. The method was tested by analyzing hair samples from forensic and clinical psychiatric patients where benzodiazepines had been prescribed during hospitalization and after care. Hair samples were obtained at discharge from the clinic and then after six months. Two-centimeter segments of the hair samples (10-30 mg) were washed once with isopropanol, three times with phosphate buffer, and again with isopropanol, dried, weighed, and digested with proteinase K before solid-phase extraction with BondElut Certify columns. Diazepam, nordiazepam, oxazepam, alprazolam, OH-alprazolam, nitrazepam, 7-aminonitrazepam, flunitrazepam, 7-aminoflunitrazepam, clonazepam, and 7-aminoclonazepam were quantitated in MRM mode using one transition for each analyte and deuterated internal standard. The calibration range was 0.125-5 ng/mg for diazepam, nordiazepam, and oxazepam and 0.025-1.0 ng/mg for the other compounds. In the hair samples analyzed, diazepam, flunitrazepam, nitrazepam, and clonazepam was detected together with their metabolites. Alprazolam was not detected in any sample. Segmental hair analysis revealed differences in drug deposition in hair before and after release from psychiatric treatment. Both increases and decreases of hair drug concentrations were seen after release even though the prescribed dose was the same. This was taken as an indication of noncompliance during the after-care period. We conclude that the extraction and LC-MS-MS procedures were adequate to detect benzodiazepines in hair and that the results indicated that segmental hair analysis might provide retrospective information about medication intake.

No abstract

The objective was to estimate the detection times and metabolite/parent compound ratios in urine after a single dose of buprenorphine. Eighteen healthy volunteers received a single dose of 0.4 mg buprenorphine sublingually. Urine samples were collected prior to dosing and at 2, 4, 6, 8 12, 24, 48, 72, and 96 h post-dose. The samples were screened using cloned enzyme donor immunoassay (CEDIA) reagent and quantitation was performed with liquid chromatography-tandem mass spectrometry (LC-MS-MS) with a cut-off of 0.5 ng/mL for buprenorphine and norbuprenorphine. The mean time of continuous positive results was 9 h (range 4 to 24 h) with CEDIA, whereas for an LC-MS-MS method it was 76 h (range 23-96 h) for buprenorphine, and for norbuprenorphine all samples were positive at 96 h. Some subjects had positive CEDIA results after a negative sample, owing to differences in creatinine concentration. The time when the ratio norbuprenorphine/buprenorphine exceeded 1 was estimated at 7 h. The metabolite/parent ratio may be used to estimate the time of intake even though the individual ratios showed an increased variation the more distant the collection time. We believe that using this ratio, rather than the actual concentrations, it is possible to compensate for urine dilution and different doses, and to improve interpretation.