Stability of diazepam in blood samples at different storage conditions and in the presence of alcohol

Atanasov, Vasil; Stoykova, Silviya; Runiov, A.; Dimitrova, T.; Aleksandrova, D. I.; Tsakovski, Stefan; Mitewa, M.

doi:10.1016/j.forsciint.2011.04.005

Cited by 18 publications

(11 citation statements)

References 13 publications

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“…According to some authors, diazepam is stable in blood and tissues , even with putrefaction , unlike other benzodiazepines , although this can depend on specimen preservation , temperature , and other factors . In our study, a C/P ratio less than 1 was observed for diazepam when comparing femoral to central blood concentrations, suggesting that diazepam is not subject to redistribution.…”

Section: Discussionsupporting

confidence: 48%

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine

Lemaire

Schmidt

Denooz

et al. 2016

Journal of Forensic Sciences

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Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites. Intracardiac blood (ICB), subclavian blood (SB), femoral blood (FB), and popliteal blood (PB) were sampled in 30 cases. To assess PMR, mean concentrations and ratios were compared. Influence of postmortem interval on mean ratios was also assessed. Results show that popliteal mean concentrations were lower than those for other sites for all three drugs, even lower than femoral blood; mean ratios suggested that the popliteal site was less subject to PMR, and estimated postmortem interval did not influence ratios except for diazepam and methadone FB/PB. In conclusion, our study is the first to explore the popliteal site and suggests that popliteal blood is less prone to postmortem redistribution.

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Section: Discussionsupporting

confidence: 48%

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine

Lemaire

Schmidt

Denooz

et al. 2016

Journal of Forensic Sciences

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“…Cultures were maintained at 37 C and 5% CO 2 in humidified incubator. Then rocuronium (final concentration 100 mM), diazepam (final concentration 50 mM) and both rocuronium and diazepam (final concentration 100 mM and 50 mM) were applied to the medium and hepatocytes were incubated for 12 h. Levels of both compounds corresponded to the values which may be reached in patients (rocuronium, see above, diazepam, levels up to 20e30 mM may be found (28)). Diazepam was added in methanol solution in concentrations for which the final solvent concentration did not exceed 0.5% (v/v) when added to incubation medium.…”

Section: Primary Cultures Of Human Hepatocytesmentioning

confidence: 99%

Interaction of rocuronium with human liver cytochromes P450

Anzenbacherová

Špičáková

Jourová

et al. 2015

Journal of Pharmacological Sciences

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Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 μM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6β-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed.

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“…In addition, oral contamination of benzodiazepines might have given unexpectedly high drug concentrations in some oral fluid samples. 30 Thus, degradation of some benzodiazepines in some samples cannot be excluded. The stability of the studied benzodiazepines in oral fluid collected with the Statsure device has been found to be good.…”

Section: Oral Fluid To Blood Ratiosmentioning

confidence: 99%

Detection of 4 Benzodiazepines in Oral Fluid as Biomarker for Presence in Blood

Gjerde

Langel

Favretto

et al. 2014

Therapeutic Drug Monitoring

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The concentration of the 4 studied benzodiazepines in oral fluid can neither be used to accurately estimate the concentrations in blood nor to correctly identify patients with blood drug concentrations below or above recommended therapeutic levels. When using analytical methods with limits of quantitation corresponding to concentrations less than 0.5 ng/mL in undiluted oral fluid, it may be used to confirm a recent intake of benzodiazepines. However, it is likely that some false negatives may occur.

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Stability of diazepam in blood samples at different storage conditions and in the presence of alcohol

Cited by 18 publications

References 13 publications

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine

Interaction of rocuronium with human liver cytochromes P450

Detection of 4 Benzodiazepines in Oral Fluid as Biomarker for Presence in Blood

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