A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue

Takatori, Takehiko; Tomii, Seibei; Terazawa, Koichi; Nagao, Masataka; Kanamori, Masao; Tomaru, Yukio

doi:10.1007/bf01369803

Cited by 12 publications

(9 citation statements)

References 14 publications

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“…Winek et al [15] demonstrated that, in rabbits, peak ethchlorvynol blood level occurs 10-30 min after intraperitoneal injection and peak BM level between 15 and 60 min. In rats, diazepam clearance appears to be slower in BM than in blood, resulting in higher and longer BM impregnation [64]. This phenomenon was also reported in rats by Watterson et al for diazepam [29] and fentanyl [26]: they assumed that accumulation occurred in BM and then in bone, followed by slow redistribution from bone to blood via BM.…”

Section: Correlation Between Bm and Blood Concentrationsmentioning

confidence: 79%

“…fatty and cellular proportion) in different bones according to age, sampling location was claimed by Winek et al [15] and McIntyre et al [2] to be a relevant factor that should be investigated. Likewise, hydrophilic or lipophilic behavior of molecules should be considered: Winek et al showed that blood/BM correlation of water soluble compound, such as methanol [23], ethanol [17], isopropanol and acetone [18], was improved correcting their concentration for water content, whereas other authors described accumulation in BM of lipophilic drugs like diazepam [2,29,64].…”

Section: Discussionmentioning

confidence: 98%

“…While mass spectrometry remains the main detection system, as reported in Table 1, other detection systems have been used, such as flame ionization detection for volatile molecules (e.g., ethanol, methanol, isopropanol). Various publications highlighted the suitability of immunological assay for qualitative [25-27, 29, 30, 62] and quantitative purposes [1, 50,63,64].…”

Section: Methodsmentioning

confidence: 99%

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State-of-the-art of bone marrow analysis in forensic toxicology: a review

et al. 2010

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Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

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Section: Correlation Between Bm and Blood Concentrationsmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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State-of-the-art of bone marrow analysis in forensic toxicology: a review

et al. 2010

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“…Therefore, the main analyte in saliva is predominantly the parent drug [55,65] and drug concentrations might be dependent on the pH value in this body fluid. The relationship between the saliva/plasma drug concentration ratio, pKa, pH and binding is expressed by the equations of Rasmussen/Matin [45].…”

Section: Biological Data On Drug Monitoring In Salivamentioning

confidence: 99%

Perspiration versus saliva - basic aspects concerning their use in roadside drug testing

Skopp

Pötsch

1999

International Journal of Legal Medicine

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Various aspects concerning the practical application and forensic interpretation of data obtained by saliva drug testing and drug monitoring from the skin surface are discussed. Basic information on the composition of saliva and skin secretions and their particular transport mechanisms, as far as known, are given. For drugs of abuse secretion into saliva is suggested to be by passive diffusion and to depend on lipid solubility, pKa, plasma protein binding and on the pH of saliva. Drug molecules from blood are considered to reach the skin surface by various routes such as by sweat and sebum as well as by inter- and/or transcellular diffusion. The role of the stratum corneum as a temporary drug reservoir exceeding positive drug findings in urine is outlined. Current data on opioids, cocaine metabolites, cannabinoids and amphetamines detected in saliva and on the skin surface are reviewed. Aspects of collection, processing and analysis of the samples for implementation in roadside testing are addressed. The requirement of test sensitivity covering the broad concentration ranges and the importance of test specificity bearing in mind that the parent drug is the main analyte present in those specimens is stressed. Theoretical and practical findings on frequently abused drugs are discussed with regard to the possibilities and limitations of drug monitoring from saliva and perspiration to support a suspicion of actual or recent drug administration.

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“…Although methods have been described for one or two benzodiazepines (sometimes the major metabolite), it seems that no screening procedure has been reported for such pharmacologically-active drugs in oral fluid. Data are available for diazepam [3,4], clobazam [5], nitrazepam [6], flunitrazepam [7], zolpidem [8] and lorazepam [9]. Because of their extensive protein binding (95-99%), benzodiazepines are only present in oral fluid in very small concentra- tions, about some ng/mL.…”

Section: Introductionmentioning

confidence: 98%