Robertson M D, Drummer O H
Victorian Institute of Forensic Medicine, Department of Forensic Medicine, Monash University, Southbank, Australia.
J Forensic Sci. 1998 Jan;43(1):5-8.
Studies were undertaken to determine the stability of nitrobenzodiazepines and their 7-amino metabolites in water and blood. At 22 degrees C nitrazepam and clonazepam were stable in sterile fresh blood containing preservative over 28 days, whereas 25% of flunitrazepam was degraded. At 37 degrees 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 degrees C. In bacterially-contaminated postmortem blood all three drugs were completely degraded over 8 h at 22 degrees 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 degrees C. All 3 nitrobenzodiazepines were stable in blood stored for up to 24 months at -20 degrees C, or 4 degrees C over 10 months. Their respective 7-amino metabolites were, however, relatively unstable at -20 degrees C with a significant loss (29%) after 2 months. At 4 degrees 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 degrees C and assayed as soon as practicable, preferably within a week of collection.
开展了多项研究以确定硝基苯二氮䓬类及其7-氨基代谢物在水和血液中的稳定性。在22摄氏度时，硝西泮和氯硝西泮在含有防腐剂的无菌新鲜血液中28天内保持稳定，而氟硝西泮有25%被降解。在37摄氏度时，9小时内所有三种药物都大量损失（29%-51%）。在这些条件下，7-氨基代谢物仅有少量损失，且母体药物和7-氨基代谢物在水中没有大量降解。在没有防腐剂的情况下，22摄氏度时新鲜血液中10天内有大量（25%-50%）母体药物损失。在22摄氏度时，被细菌污染的死后血液中，所有三种药物在8小时内完全降解，几乎所有药物都完全转化为各自的7-氨基代谢物。这些代谢物在22摄氏度时45小时内也有部分降解（10%-20%）。所有三种硝基苯二氮䓬类在-20摄氏度下储存长达24个月或在4摄氏度下储存10个月的血液中都是稳定的。然而，它们各自的7-氨基代谢物在-20摄氏度下相对不稳定，2个月后有显著损失（29%）。在4摄氏度时，1个月后损失21%。发现冻融不影响硝基苯二氮䓬类和7-氨基代谢物的浓度。这些结果表明，硝基苯二氮䓬类及其代谢物在血液中化学和代谢上是不稳定的。我们建议，为测定硝基苯二氮䓬类而采集的血液应使用氟化钠保存，储存在-20摄氏度，并尽快进行检测，最好在采集后一周内进行检测。
