Study of the distribution of antidepressant drugs in vitreous humor using a validated GC/MS method.

Vitreous humor has become in recent years an important alternative biological fluid in forensic toxicological analysis especially for the investigation of cases where alcohol and drugs of abuse are involved but there is limited scientific information regarding the distribution of antidepressant drugs in this material. This work aimed to study the distribution of antidepressant drugs in vitreous humor and to estimate the blood/vitreous humor concentration ratios of these drugs. For this purpose, a GC/MS method for the simultaneous determination of 9 antidepressant drugs, namely amitriptyline, nortriptyline, citalopram, clomipramine, fluoxetine, maprotiline, mirtazapine, sertraline and venlafaxine, and 4 of their metabolites, namely desmethylmaprotiline, desmethylmirtazapine, desmethylsertraline, O-desmethylvenlafaxine, was developed and validated. The developed method includes solid-phase extraction followed by derivatization with Heptafluorobutyric Anhydride. For all analytes, LOD and LOQ were 1.50 and 5.00ng/mL, respectively, and the calibration curves were linear within the dynamic range of 5.00-500.0ng/mL (R2≥0.990). The absolute recovery was found to be ≥86.3 % for all analytes. The accuracy (%Er) was found to range between -6.58 and 6.18 %, whereas the precision (%RSD) was less than 10.9 % for all analytes. The developed method was successfully applied to vitreous humor samples from 43 blood positive cases for antidepressant drugs. Whenever antidepressant drugs were detected in blood, they were also detected in the respective vitreous humor samples. The vitreous humor/blood concentration ratios were also calculated and were found to range from 0.04-7.07. Citalopram, mirtazapine, and its metabolite desmethylmirtazapine as well as venlafaxine and its metabolite O-desmethylvenlafaxine were the most identified substances in these samples (n≥4) and their results were better statistically evaluated. Our results suggest that vitreous humor could be an appropriate matrix for the determination of antidepressants in postmortem toxicology.

Validated method for the simultaneous determination of methadone and its main metabolites (EDDP and EMDP) in plasma of umbilical cord blood by gas chromatography-mass spectrometry.

A sensitive and specific GC/MS method for the determination of methadone (MDN) and its two main metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP), in plasma samples obtained from venous and arterial umbilical cord blood and maternal blood has been developed, optimized and validated. Specimen preparation includes protein precipitation with acetonitrile and simultaneous solid-phase extraction of the three analytes. Methadone-d9 was used as internal standard for the determination of MDN and EMDP, while EDDP-d3 for EDDP. Limits of detection were 0.6 microg/L for MDN and 0.3 microg/L for EDDP and EMDP, while limits of quantification were 2.0 microg/L for MDN and 1.0 microg/L for EDDP and EMDP. The calibration curves were linear up to 2000 microg/L for MDN and up to 1000 microg/L for EDDP and EMDP. Absolute recovery ranged from 94.8 to 99.7% for all three analytes. Intra- and interday accuracy was less than 5.3 and 5.5%, respectively, while intra- and interday precision was less than 3.5 and 5.0%, correspondingly, for all analytes. The method proved suitable for the determination of MDN and its two main metabolites in plasma samples obtained from umbilical cord and maternal blood of a woman participating in a MDN maintenance program, during the prenatal and postpartum period.

Driving under the influence in Greece: a 7-year survey (1998-2004).

Alcohol is one of the main causes of traffic accidents worldwide. Its use decreases significantly the driving ability of an individual increasing in this way the possibilities of their involvement in motor-vehicle accidents. The above possibilities are increased when a psychoactive substance has been taken in combination with alcohol due to their synergistic effect. The Laboratory of Forensic Medicine and Toxicology of the University of Athens is authorized to perform the toxicological investigation of traffic accidents that happen in the southern part of Greece. The objective of the present study was to identify the prevalence of alcohol and other psychoactive substances among drivers involved in road traffic accidents in Greece during the period 1998-2004. Alcohol was detected in the blood of about 37% of the drivers involved in traffic accident during the years 1998-2000. The detection of alcohol was lower (29%) in the years 2001-2004. Cannabis, benzodiazepines, opiates, and cocaine were found in 4%, 4%, 4% and 1% of the total number of cases, respectively. The above values were compared with those of a previous study concerning the period 1995-1997 and the reasons for the reduction of the number of alcohol-related traffic accidents during the last years are discussed.

Cardiovascular disease and drowning: autopsy and laboratory findings.

INTRODUCTION: The purpose of this report is to describe the main autopsy and laboratory findings from a large number of drowning victims in Greece. METHODS: A retrospective analysis was carried out of the consecutive cases of drowning victims autopsied in our department during the period 1997-2004. RESULTS: A total of 197 submersion cases were referred to the Department. In 168 cases drowning was considered as the cause of death. In 82 cases (49%) significant histopathological findings from the cardiovascular system were present. Alcohol was found in 21 cases (13%) and psychoactive substances in 4 cases (2%). Food was found in the stomach of 45 drowning victims (27%). Men (65%) and elderly people (60 years and older, 74%) made up the majority of drowning victims. In 29 submersion cases the cause of death was other than drowning; in 25 of these cases death was attributed to cardiovascular disease (complication of coronary artery disease, 23 cases; dissecting aortic aneurysm, 1 case; cerebral stroke, 1 case). CONCLUSIONS: The great majority of drowning victims are the elderly and men. Moreover, in a considerable number of submersion cases cardiovascular disease was related to the death, either as a contributing factor, or as the cause of death.