Stability of benzodiazepines in formaldehyde solutions

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.