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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 25,
Number 3, April 2001, pp. 166-173
Stability
of Benzodiazepines in Formaldehyde Solutions
Timothy S.
Tracy, Blanche F. Rybeck, Devona G. James, James B. Knopp, and Peter M. Gannett
Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia
University, Morgantown, West Virginia
Benzodiazepine-type drugs are used in the treatment of a number
of pathologic disorders, but they may be implicated in forensic toxicology cases
because of their abuse potential. Occasionally, it becomes necessary to measure
drug levels following exposure to formaldehyde (postembalming or after tissue
storage) if drug involvement was not previously suspected. Virtually no information
exists on the decomposition of benzodiazepines in the presence of formaldehyde
(the active ingredient in many embalming fluids), yet formaldehyde is known
to be highly reactive, particularly with nitrogen-containing compounds. In order
to evaluate the effects of formaldehyde on benzodiazepines, 10 benzodiazepine
drugs were exposed to various concentrations of formaldehyde and various pH
conditions (to simulate potential postembalming conditions), and the decomposition
of each drug was measured by high-performance liquid chromatography over a 30-day
period. The decomposition rates of all but one of the benzodiazepines were accelerated
(to differing degrees) by formaldehyde as compared to controls, and this decomposition
was in several cases both pH and formaldehyde concentration dependent. Thus,
forensic examiners must be particularly cautious when attempting to determine
benzodiazepine concentrations postembalming because the compound may have reacted
with formaldehyde to form other products not inherently obvious analytically.
Determination of these reaction products will serve to provide alternate analytes,
allowing for establishment of accurate conclusions during forensic analyses.
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