Paul B.D., Addison J. W.
Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology, Rockville, MD 20850, USA
Little is known about metabolic profiles of the concurrent use of smoking cocaine (COC) and drinking alcohol. When COC is smoked, methyl ecgonidine (MED) is consumed as a pyrolytic compound. The amount of MED inhaled depends on the purity of cocaine and the temperature of the smoking device. At temperatures of 255-420 °C, the amount of COC converted to MED is 50-80 %. Consumption of ethanol with smoking COC may initiate metabolic ethanol-transesterification of MED to ethyl ecgonidine (EED).
Both esters are likely to produce ecgonidine (ED) as a major metabolite. The presence of EED and an oxi-dative metabolite, nor-ecgonidine (NED), in urine has been investigated.
Urine specimens submitted to us for forensic investigation and tested positive for COC by immunoassay were selected in this study. Specimens from four postmortem cases and three living persons were extrac-ted by a silica-based -Cg and -SO3H solid-phase extraction technique and analyzed by gas chromatogra-phy-mass spectrometry using selected-ion monitoring. The ions for MED were m/z 181, 166 and 152, and for EED were m/z 195, 166, and 138. The ED and NED were detected as pentyl derivatives using ions m/z 237, 208, and 138 for ED, and m/z 293, 264, and 236 for NED.
In all four PM and three LV specimens MED (10-399 mg/mL), ED (125-2937 ng/mL), and NED (3.1-163 ng/mL) were detected. EED was detected in all PM specimens (12-39 ng/mL) and in one LV specimen (3.7 ng/mL). To support ethanol-transesterification of MED to EED, the specimens were tested for etha-nol and found to contain 40-332 mg/dL of ethaetha-nol in the EED-positive PM specimens. Ethaetha-nol was not detected in the EED-positive LV specimen. It is possible that the detection time of EED is longer than that of alcohol. Typical concentrations of MED and its metabolites are ED>MED>NED>EED. COC (129-4564 ng/mL) and benzoyiecgonine (1114-277,819 ng/mL) were detected in all specimens. The molar ratios of the two major non-pyrolytic and pyrolytic metabolites in the specimens vary considerably (BZ:ED; 961:14 to 4:13 umol/L). The major reason is likely due to the variation in pyrolysis of COC to MED. While the presence of EED, ED, or NED in urine is an indication of smoking cocaine, the presen-ce of EED is a strong indication of concurrent use of smoking cocaine and drinking alcohol.
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Analytical aspects of Volatile Substance Abuse (VSA ): about a case report
Gaulier J.M.( I ). Faict T,W.(3), Sayer H,">, Fabre M.<3), Lachâtre G.(l)(1) Service de Pharmacologie et Toxicologie, CHU Dupuytren, 87042 Limoges - France (2) Médecin légiste, Expert près la Cour d'Appel, 63000 Clermont-Ferrand - France (3) Centre antipoison, 31059 Toulouse - France
Volatile Substance Abuse (VSA) represents an increasing phenomenon in our society owing to the availa-bility and the low cost of the related compounds. In forensic toxicology, the main difficulties are due to evaporation of these compounds from post-mortem samples and to the lack of reference data for interpre-tation. Through a case report, the authors present the substances of interest, propose analytical methods and illustrate the difficulties of analytical investigation for VSA,
A 17 year-old boy, student in a chemistry institute, was found dead in his bedroom by his mother at day-break. The corpse was found in sitting position on a bed, a plastic bag placed on the head without any links around the neck. The assumptions of a homicide or a suicide were ruled out by the officers in charge of the investigation. Several chemical substances (as pure substances or in domestic/industrial mixtures) such as oxidants (ferric chloride, ethyl methyl ketone peroxide, ...), acids (phosphoric acid, acetic acid,...) and petroleum derivatives (acetone, ethoxyethyl, developer for photography, stain remover called "eau écarla-te", ...) were found in the belongings of the young boy. The absence of external lesions evocative of an aggression was established by the autopsy performed two days later. Autopsy findings included serious pulmonary lesions associated with hemorrhagic digestive ulcerations. The biological samples collected and the plastic bag were sent to the laboratory for forensic toxicological analysis.
A large screening of drugs and toxic compounds in blood and urine was performed using both high-per-formance liquid chromatography coupled to a diode array detector (HPLC-DAD) and gas chromatography - mass spectrometry (GC-MS). More selective analyses for several classes of drugs of abuse were carried out with various ad-hoc methods using HPLC-DAD, liquid chromatography-electrospray-mass spectro-metry (LC-ES-MS) and GC with various detection modes. In particular, a headspace (HS) - gas chroma-tography - mass spectrometry (GC/MS) technique was used to screen for residues of volatile substances on the surface of the plastic bag and for volatile substances and metabolites in blood, lungs, urine and gas-tric content.
The main analytical findings was the presence of alkanes (heptane, methyl-2- pentane, methyl-3-hexane, methylcyclohexane) in the gastric content. Literature data, VSA practices, the long time-delay elapsed between death and autopsy, preservation of the biological samples before analysis, and in-lab experiments on evaporation of volatile substances were taken in account to interpret this result. The present fatality was attributed to a sudden sniffing death syndrome certainly due to a VSA with a gasoline-based cleaner like
"eau écarlate", associated with a hypoxic recreation practice using a plastic bag.
References :
1- Fukunaga T., Yamamoto H., Tanegashima À., Yamamoto Y, Nishi K., Forensic Sci Int, 1996, 82 : 193-200 2- Barriere A., Gonzalez D,, Meyrieux J., Dissait F., Cah Anesthesiol, 1987, 35 : 125-7.
Annales de Toxicologie Analytique, vol. XIV, n° 3, 2002
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Determination of nalbuphine in samples from nalbuphine abusers and rat
Chung FL Park M., Han E., Choi H., Sohn H., Choi C , Yoo Y.National Institute of Scientific Investigation, 331-1 Shinwol-dong, Yangchon -ku, Seoul 158-707, Korea Nalbuphine is a partial agonist and narcotic with potent analgesic properties. Because of the limited avai-lability of methamphetamine, the abuse of nalbuphine as an alternative for methamphetamine began in
1991. Even though the effects of nalbuphine and methamphetamine are different, drug abusers considered them similar because they are administered in a same way of iv administration. Due to its prevalent abuse, the government started to control it as a psychotropic agent since January 2001.
To establish the rapid determination of nalbuphine in urine, GC/MS method for nalbuphine was developed to apply to drug abuser's urine. The urinary excretion of nalbuphine was studied after ip administration of nalbuphine to rats. For human urine, the concentration of nalbuphine was measured and the level of cut-off for positive result was studied. For pharmacokinetic study, venous blood samples were drawn at 1, 5, 10, 15, 30, 45, 60, 90 and 120 minutes after iv administration of 2 mg/kg nalbuphine to rats.
Nalbuphine and its metabolites in urine were hydrolyzed and extracted by solid- phase extraction. They were well resolved by GC/MS after TMS derivatization. Two metabolites, nornabuphine and 6-ketonalbu-phine were detected in both drug abuser and rats' urine. The percentages of recovery were found to be
100.7 %, 109.0 % at 1 and 5 ug/ml with CV value of less than 10 % in rat urine. Urinary excretion of nal-buphine revealed that 93.1 % of nalnal-buphine was excreted in 6 h and no nalnal-buphine was detected in rat urine collected from 24 to 48 h.
In human urine the cut off value of 0.1 ug/ml was set for positive result and 0.05 ug/ml of nalbuphine was detected by this method. By this method, in 2000, nalbuphine was detected in 30 urines, while in first three months of 2001, 138 urines were positive for nalbuphine. The combination of nalbuphine with metham-phetamine and cannabis was also determined in 14 and 30 specimens in 2000 and 2001 respectively.
Pharmacokinetic data revealed the elimination half-life of 21.23 ± 8.99 min, C max of 1055.67 ± 422.23 ng/ml and AUC of 80526.7 ± 73079 ng.min/ml after 2 mg/kg dosing to rats.
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Substance abuse and in-custody deaths
Blaho K.E.. Beauvois E. J.Department of Emergency Medicine, UTMG, Memphis, TN , USA
In custody deaths represent a potentially costly legal forum. Despite common accusations of improper care, the majority of in custody deaths are not unexpected and are not a result of improper care. We retros-pectively reviewed 27 in custody deaths from for a local law enforcement agency. All were male, the mean age was 44 ± 9 years with an age rage of 22-64 years. Of the 27 inmates who died in custody, 24 had a history of substance abuse, most notably alcohol (19/21). Of the 19 with alcohol abuse, nearly half had end stage liver disease and/or hepatitis. Cocaine use was documented in 10 patients, opioid use in 4. Twenty four deaths were ruled as natural, three were of unknown cause. All 27 patients had prior admissions to the hospital and were discharged back to jail. In the 27 cases we reviewed, all but 3 deaths are attributable to substance abuse, most notably alcohol and/or cocaine. The most common mechanisms of death is sud-den cardiac death, presumably from arrhythmias. Other modes of death include seizures and cerebral vas-cular accidents. Substance abuse is a significant risk factor for in custody deaths in the midsouth portion of the United States.