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).

Comments

Scanned, with permission from the author, from the original print version, which resides in University Archives.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-1-2017

Included in

Pathology Commons

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