In vitro reaction of formaldehyde with fenfluramine: conversion to N-methyl fenfluramine.
(1/19)
Embalming is common, and it can create problems for the forensic scientist if a drug has been the cause death and this drug is also reactive toward the embalming fluid. Previous studies have focused on the tricyclic amines nortriptyline and desipramine. In the presence of formaldehyde, a typical component of embalming fluid, either of these two compounds can be rapidly converted to their methylated derivatives amitriptyline and imipramine, respectively. We have begun a larger project designed to determine the reactivity and reactions of a wide range of drugs with formaldehyde. We report here our results from fenfluramine, which, like the tricyclic amines, is reactive towards formaldehyde and is converted into its N-methyl derivative. The rate of conversion is dependent upon pH and formaldehyde concentration. Up to 100% conversion in 24 h was observed. In addition, we have also devised a simplified procedure for monitoring this process that may be useful for others working in this area. Finally, we note that the reactions of fenfluramine studied here and of amines in general with formaldehyde need to be considered when performing postmortem/postembalming forensic analysis. (+info)
In vitro reaction of barbiturates with formaldehyde.
(2/19)
Barbiturates are widely used as sedatives, hypnotics, and antiepileptics, and, when coupled with their narrow therapeutic index, the probability that their use will result in accidental or intentional death is significant. When barbiturates are implicated in a murder or suicide, analysis for their presence is often required. Under certain conditions, barbiturates are quite stable, but conditions found in vivo immediately after death or after embalming may promote barbiturate decomposition. If extensive decomposition occurs, analysis for them may be difficult or impossible. Here, the stability of three representative barbiturates, under conditions that model those likely to prevail in vivo shortly after death and after embalming, have been studied. Solutions of phenobarbital were found to slowly decompose in water over the pH range of approximately 3.5 to 9.5. More rapid decomposition occurred at higher pH, and 2-phenylbutyric acid was the main decomposition product. Formaldehyde (5-20%) accelerated the decomposition rate 3-10-fold such that phenobarbital decomposition could be complete after 30 days. In contrast, pentobarbital decomposed roughly 10 times more slowly and secobarbital did not detectably decompose under any of the conditions studied. Thus, certain barbiturates may partially or completely decompose in vivo after death, especially after embalming, and thus analysis for them may lead to false negatives. However, this work shows that analysis for the parent barbiturate or its predicted decomposition product may provide data that will reduce the likelihood of false negatives. (+info)
MR imaging visualization of the cerebral microvasculature: a comparison of live and postmortem studies at 8 T.
(3/19)
SUMMARY: In this study, we compared 8-T gradient-echo MR images of the microvasculature in the live human brain with images of the unembalmed and embalmed postmortem brain. Small vessels were well visualized in the live brain and even better seen in the unembalmed postmortem brain, but they could not be visualized in the embalmed postmortem brain. These findings are important for direct comparisons of the microvasculature on 8-T MR images and on histologic sections. (+info)
Applied anatomy of the superior vena cava-the carina as a landmark to guide central venous catheter placement.
(4/19)
BACKGROUND: Cardiac tamponade is a serious complication of central venous catheter (CVC) insertion. Current guidelines strongly advise that the CVC tip should be located in the superior vena cava (SVC) and outside the pericardial sac. This may be difficult to verify as the exact location of the pericardium cannot be seen on a normal chest x-ray. The carina is an alternative radiographic marker for correct CVC placement, suggested on the basis of studies of embalmed cadavers. METHODS: We set out to confirm this radiographic landmark in 39 fresh cadavers (age 58.4 (3.4) (mean and SE) yr) and to compare the results with those from ethanol-formalin-fixed cadavers. RESULTS: We found that the carina was 0.8 (0.05) cm above the pericardial sac as it transverses the SVC. In no case was the carina inferior to the pericardial reflection and our study confirmed the previous findings. All the measured distances were significantly greater in fresh cadavers. CONCLUSIONS: We confirm that the carina is a reliable, simple anatomical landmark that can be identified in vivo for the correct placement of CVCs outside the boundaries of the pericardial sac. (+info)
Conversion of methamphetamine to N-methyl-methamphetamine in formalin solutions.
(5/19)
Embalming is common, and yet it can create problems for the forensic scientist if a drug has been the cause of death and if this drug is also reactive toward the embalming fluid. Previous studies have focused on the amines such as nortriptyline, desipramine, and fenfluramine. In the presence of formalin, a typical component of embalming fluid, these compounds can be rapidly converted to their methylated derivatives amitriptyline, imipramine, and N-methyl-fenfluramine, respectively. We have begun a larger project designed to determine the reactivity and reactions of a wide range of drugs with formalin and have extended it to amphetamines. We report here our results from methamphetamine, which is converted into its N-methyl derivative in the presence of formalin. The rate of conversion is dependent upon pH and formalin concentration with the greatest conversion occurring under basic conditions and the highest formalin concentration. Up to 100% conversion in 24 h was observed under certain conditions. When studied in human tissue exposed to methamphetamine and treated with formalin, again, conversion to N-methyl-methamphetamine was readily apparent as early as 30 min after exposure to formalin. Finally, we note that the reactions of methamphetamine with formalin studied here are probably general and should be considered when performing postmortem/postembalming forensic analysis. (+info)
Methylation of 3,4-methylenedioxymethamphetamine in formalin-fixed human liver tissue.
(6/19)
3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a commonly consumed recreational drug. As is the case with most secondary amines, MDMA reacts with formaldehyde under acidic conditions to form tertiary amines. This reaction is likely to occur in formalin-fixed tissue. In formalin solutions, MDMA is methylated producing 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDA). MDDA standard was synthesized by treating methylenedioxyamphetamine HCl in formaldehyde solution. Structure confirmation was by electrospray ionization-mass spectrometry (MS) and MS-MS. Randomly chosen human liver pieces (100-200 mg) were injected with 2 microg of MDMA HCl. The liver pieces in centrifuge tubes were covered with 200 microL of formalin solution (20% v/v), held at room temperature for 24 h, and then homogenized. The resulting suspension was sonicated for 5 min and then centrifuged. Controls consisted of substitution of 200 microL of water in place of formalin solution. Supernatant aliquots (10 mciroL) were added to 500 microL of 0.1% formic acid in acetonitrile for MS analysis. Positive ion electrospray spectra recorded in MS, MS2, and MS3 modes were used to confirm the presence of methylated MDMA. Liver tissue containing added MDMA HCl but not treated with formalin did not show a detectable level of methylated MDMA. (+info)
Conversion of sertraline to N-methyl sertraline in embalming fluid: a forensic implication.
(7/19)
Zoloft (sertraline hydrochloride) is one of the antidepressant medications used to treat depression, obsessive-compulsive disorder, and social anxiety disorder. The practice of embalming a cadaver is common, yet it may create problems for forensic toxicologists if the case was not previously suspected to involve drug overdose. According to the Eschweiler-Clarke reaction, drugs containing a secondary amine group react with formaldehyde to give N-methyl derivatives. Sertraline has a secondary amine group; therefore, we predicted that it may react with formalin to give N-methyl derivatives. The stability of sertraline in formalin solution was studied at three different concentrations (5%, 10%, and 20%) and at three different pHs (3.0, 7.0, and 9.5) for a period of 30 days. Setraline and its degraded products were extracted by liquid-liquid extraction using chloroform, and the concentrated extracts were analyzed by gas chromatography-mass spectrometry using electron impact ionization mode. The rate of conversion is rapid at higher pH. Sertraline was totally converted to the N-methyl derivative after 30 days in 10% and 20% formalin solutions at neutral and basic conditions. Therefore, forensic toxicologists should be cautious when performing a death investigation if formalin solution is the only sample available for analysis. This work shows that analysis for parent drug or its N-methyl derivative may provide data that will reduce the likelihood of false negatives. (+info)
Stability study of fluoxetine in formalin-fixed liver tissue.
(8/19)
In the present work, we report conversion of fluoxetine (Prozac), a novel anti depressant to N-methyl fluoxetine in formalin fixed liver tissue. Earlier studies indicate that drugs containing secondary amino group will react with formalin to form corresponding N-methyl derivatives. Even though embalming cadavers is common, it may create problems for forensic toxicologists if a case was not previously suspected. In formalin solutions, fluoxetine is methylated producing N-methyl fluoxetine. N-Methyl fluoxetine standard was synthesized by treating fluoxetine in formaldehyde solution. The structure confirmed by (1)HNMR and gas chromatography-mass spectrometry in electron impact ionization mode. Randomly chosen rat liver pieces (200-250 mg) were injected with 100 microg of Fluoxetine. The liver pieces were covered with three different concentrations of formalin, 5%, 10%, and 20%, and at three different pHs, 3.0, 7.0, and 9.5. The reaction was studied for a total period of 30 days, and the reaction products were monitored on days 0, 4, 14, and 30 days. The study indicates that the rate of conversion of fluoxetine to its N-methyl derivative increased with increase in the concentration of formalin and pH of the solution. The conversion is rapid at higher pH values. Fluoxetine was totally converted to its N-methyl derivatives after 30 days in 20% formalin at pH 9.5. Therefore, analysis for parent drug or its N-methyl derivative in embalmed tissues may provide data that will reduce the likelihood of false negatives. (+info)