Defense Date
2023
Document Type
Directed Research Project
First Advisor
Amber Burns
Second Advisor
Catherine Savage
Third Advisor
Dr. Michelle Peace
Fourth Advisor
Dr. Stephen Raso
Abstract
Analysis of pharmaceutical samples comprise a large percentage of the casework in forensic controlled substances laboratories. Due to the similarities in visual appearance of many illicit pharmaceutical samples and their legitimate pharmaceutical preparations, as well as the emerging complexities in the drug landscape, an accurate and rapid confirmation tool is desired for the identification of the active ingredient(s) in pharmaceutical samples. To reduce the time of analysis of pharmaceutical samples, a Direct Analysis in Real Time coupled Time of Flight Mass Spectrometer (DART-TOF-MS) was used to identify the active ingredient(s). The incorporation of tetracaine as an internal standard was investigated for the confirmation of samples. The lower limit of detection for the method was established. The selectivity of this method was evaluated by comparing drugs with identical molecular masses using in-source collision induced dissociation (is-CID) fragmentation. Principal component analysis (PCA) was used to differentiate spectra of drugs with identical mass and Multivariate Analysis of Variance (MANOVA) was performed to assess significance. Mass assignment inter-day and intra-day reproducibility tests were performed on the DART-TOF-MS spectra. Box plots of the reproducibility data were made, and Analysis of Variance (ANOVA) was performed to assess significance. Finally, the results of this technique were compared to gas chromatography coupled mass spectrometry (GC-MS), an established analytical protocol, to assess the viability of DART-TOF-MS as a confirmation tool in pharmaceutical analysis. This study determined that incorporating tetracaine as an internal standard did not significantly affect the DART-TOF-MS spectra and the ability to differentiate and identify controlled substances in pharmaceutical samples. Incorporating an internal standard improves data integrity and reduces challenges associated with qualitative analysis of pharmaceutical samples using DART-TOF-MS. Using DART-TOF-MS may pose challenges in distinguishing isobaric compounds, like fentanyl and fentanyl isomers. While not observed in this study, samples containing tramadol may interfere with the tetracaine standard. This validation shows that performing a physical identification of the markings on a pharmaceutical preparation, followed by DART-TOF-MS to confirm the active ingredient(s), is an acceptable alternative to confirming the active ingredient(s) using GC-MS. This new workflow will effectively reduce analysis time thereby reducing case backlog. The results of this study will be used to assist the Maryland State Police Forensic Science Division: Controlled Dangerous Substances Unit in their method validation study establishing DART-TOF-MS for the confirmation of pharmaceutical preparations.
Rights
© The Author(s)
Is Part Of
VCU Master of Science in Forensic Science Directed Research Projects
Date of Submission
4-28-2023