In Vitro Reaction of Formaldehyde with Drugs and Poisons: Identification of the Conversion Products

Yokchue, T. and Anderson, R. (2014) In Vitro Reaction of Formaldehyde with Drugs and Poisons: Identification of the Conversion Products. In: World Forensic Festival 2014, Seoul, Korea, 12-18 Oct 2014,

Abstract

In tropical countries, formalin, the active ingredient of which is formaldehyde, is injected into cadavers as an embalming solution to reduce body decomposition and preserve the body for a longer time. All drugs present in the body will be exposed to formaldehyde, a highly reactive substance that can chemically react with analytes, resulting in decreasing concentrations of the original compounds and producing one or more new substances. Occasionally, in some cases, formalin-blood, formalin-fixed tissue or embalming fluid is required for drugs analysis, and an analysis of these samples may create a false negative or false positive because of the reaction between drugs and formaldehyde. Previous studies on the chemical reactivity between formalin solution and drugs demonstrated that many drugs are unstable in formalin-fixed tissue and or the formalin solution in which the tissue is stored. In particular, primary and secondary amines can react with formaldehyde to form secondary and tertiary amines by the Eschweiler–Clarke reaction. The present study was aimed at quantification of the original drugs and identification of their degradation products in formalin solution. In order to evaluate the effect of formaldehyde on drugs and poisons, a range of model compounds was used, including amphetamine-type stimulants (amphetamine, methamphetamine, and 3,4-methylenedioxy-N-methamphetamine (MDMA)), benzodiazepines (alprazolam and diazepam), opiates (morphine, hydromorphone, codeine, and hydrocodone) and a carbamate insecticide (carbosulfan), which are often associated with cases of suicide, homicide, accidental poisoning and road traffic accident because of their toxicity and potential for abuse. Spiked samples in 10% formalin solution (with no pH adjustment) were stored at room temperature and analysed at selected times over 30 days. The original drugs were quantified and their degradation products in formalin solution were identified and confirmed by gas chromatography-mass spectrometry (GC/MS) and liquid chromatography - triple quadrupole mass spectrometer (LC/MS/MS).The results show that amphetamine (a primary amine) is methylated producing methamphetamine and methamphetamine (secondary amine) produces dimethylamphetamine (DMA). MDMA is methylated producing 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDMA). For opiates, hydrocodone rapidly changes to a more polar compound that gives an MH+ at m/z 360. Hydromorphone also changes to more polar compounds with MH+ at m/z 316 and 346. Codeine and morphine are stable in formalin solution. Furthermore, open-ring alprazolam (5-chloro-[2-(3-aminomethyl-5-methyl-1,2,4-triazol-4-yl]benzophenone) was observed as the hydrolysis product of alprazolam. Carbosulfan is completely hydrolysed to carbofuran within 24 h. The forensic toxicologist should consider the degradation products as potential target analytes when performing drugs analysis in embalming samples.

• Item Type: Conference Proceedings
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Anderson, Dr Robert
• Authors: Yokchue, T., and Anderson, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing

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