Stability of Nitrobenzodiazepines in Postmortem Blood

    Volume 43, Issue 1 (January 1998)

    ISSN: 0022-1198

    CODEN: JFSOAD

    Published Online: 1 January 1998

    Page Count: 4


    Robertson, MD
    Monash University, Southbank,

    Drummer, OH
    Monash University, Southbank,

    (Received 1 July 1996; accepted 25 April 1997)

    Abstract

    Studies were undertaken to determine the stability of nitrobenzodiazepines and their 7-amino metabolites in water and blood. At 22°C nitrazepam and clonazepam were stable in sterile fresh blood containing preservative over 28 days, whereas 25% of flunitrazepam was degraded. At 37°C all three drugs were substantially lost over 9 h (29–51%). There was only a small loss observed for the 7-amino metabolites and no substantial amounts of parent drug and 7-amino metabolite were degraded in water under these conditions. In the absence of preservative substantial amounts (25–50%) of parent drugs were lost in fresh blood over 10 days at 22°C. In bacterially-contaminated postmortem blood all three drugs were completely degraded over 8 h at 22°C with almost all drug completely converted to the respective 7-amino metabolite. These metabolites were also partially degraded (10–20%) over 45 h at 22°C. All 3 nitrobenzodiazepines were stable in blood stored for up to 24 months at −20°C, or 4°C over 10 months. Their respective 7-amino metabolites were, however, relatively unstable at −20°C with a significant loss (29%) after 2 months. At 4°C a 21% loss occurred after 1 month. Freeze/thawing was found not to affect the concentration of nitrobenzodiazepine and 7-amino metabolites. These results show that the nitrobenzodiazepines and their metabolites are unstable chemically and metabolically in blood. We advise that blood collected for the purpose of nitrobenzodiazepine determinations should be preserved with sodium fluoride, stored at −20°C and assayed as soon as practicable, preferably within a week of collection.


    Paper ID: JFS16081J

    DOI: 10.1520/JFS16081J

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    Author
    Title Stability of Nitrobenzodiazepines in Postmortem Blood
    Symposium , 0000-00-00
    Committee E30