DOI
https://doi.org/10.25772/CA72-FR84
Defense Date
1982
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Pathology
First Advisor
Robert V. Blanke
Second Advisor
James C. Valentour
Abstract
The delay that occurs between specimen acquisition and analysis in clinical and forensic toxicology requires the establishment that no changes in drug concentration have occurred during this timed interval. In this research, severai groups of common drugs were examined for stability in serum, blood and tissues at room temperature and at 4°C. Specifically, benzodiazepines, barbiturates, lidocaine, procainamide and nortriptyline were studied. Decreases were found in the following drugs: chlordiazepoxide, norchlordiazepoxide, demoxepam, and nitrazepam. No changes were found in the other drugs. More detailed work was performed on chlordiazepoxide (CDP). Two breakdown products, demoxepam and nordiazepam (ND) were identified and quantitated. A series of experiments at various pH's in the presence and absence of fluoride/oxalate (F-/C2O2=) were undertaken to examine chemical and microorganism effects on CDP breakdown in blood and buffer. At pH5, the rate of CDP breakdown was the same in blood and buffer and no nordiazepam was formed in either medium. This was determined by comparing the slopes of ln(CDP) vs. time for each condition; the slopes were about -.06 for each. All slopes are in (days)-1. At pH 6.5 and pH 8, in the absence of F-/C2O2=, CDP was less stable in blood than buffer (slopes of -.13 and -.27 versus -.036 and -.039) and ND was formed in the blood. At these pH's, F-/C2O2= stabilized CDP in blood such that it was more stable than buffer (slopes of -.0047 and -.0066 versus -.038 and -.036).
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-1-2017
Comments
Scanned, with permission from the author, from the original print version, which resides in University Archives.