Semester

Spring

Date of Graduation

2010

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Chemistry

Committee Chair

Suzanne Bell.

Abstract

gamma-Hydroxybutyrate (GHB) and gamma-hydroxyvalerate (GHV) are suspected agents of drug facilitated sexual assault. Research is needed to improve detection methods for both drugs for a range of instrumentation commonly available to forensic chemists. GHB evidence may be introduced to the laboratory in the form of a powder, solution, beverage, or biological sample; thus a key theme of this research is overcoming matrix effects for comprehensive analyses. As GHV is not commercially available, it was synthesized for analysis via base hydrolysis of gamma-valerolactone (GVL). The results of the synthesis were confirmed using infrared (IR) spectroscopy and proton nuclear magnetic resonance (H1NMR) spectrometry. As no presumptive test is currently available to forensic laboratories for GHB, methods were developed to screen for GHB and GHV using microcrystal testing and ion mobility spectrometry (IMS). The microcrystal test investigated was found to be sensitive (to 0.01% w/v) and selective (based on crystal shape and angle measurement) for both GHB and GHV in solid forms, solutions, or beverages. Further, X-ray diffraction (XRD) was used to confirm the identity and placement of GHB and GHV in the crystals formed. Application of XRD to drug crystal analysis is novel and may reinvigorate this collection of fast and simple screening techniques. The second screening technique, IMS, was found to be sensitive (positive alarm response at 3ppm) and selective for GHB analogs and GHV analogs in solutions and toxicological samples. The published IMS data was later chosen as a Selected Article on the Analysis of Drugs of Abuse in Biological Specimens (July--December 2006) by the United Nations Office on Drugs and Crime. To complement the investigated screening technique, a sensitive confirmatory technique, gas chromatography-mass spectrometry, was validated (limit of detection 1pg on column, 100ppm in solution) for GHB and GHV in beverages. Lastly, the metabolism of GHB in the presence of alcohol was studied to improve understanding of the effects of coadministration. A literature search revealed that coadministration results in effects that are greater than additive; however, the mechanics of this interaction continue to elude forensic toxicologists. In this study, the basic cytosolic metabolism of GHB was studied to look for trends in GHB elimination in the presence of ethanol. Although no interference constant was able to calculated, the presence of alcohol was shown to decrease production of NADPH, a product of GHB metabolism. A decrease in product further promotes the theory that ethanol inhibits at least part of the metabolism of GHB.

Download

Share

COinS