Semester

Spring

Date of Graduation

2019

Document Type

Thesis

Degree Type

MS

College

Eberly College of Arts and Sciences

Department

Forensic and Investigative Science

Committee Chair

Suzanne Bell

Committee Co-Chair

Luis Arroyo

Committee Member

Luis Arroyo

Committee Member

Jonathan Boyd

Abstract

Detection of SCs in body fluids continue to be a challenge because of limited metabolism data, lack of standards and reference mass spectrometry data. In vivo and in vitro experiments help elucidate metabolite markers for novel psychoactive substances and can prompt synthesis of standards to verify proposed metabolites. In this study, metabolism of three SCs N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamine (PX-1), N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluropentyl)-1H-indazole-3-carboxamide (PX-2), and N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (PX-3) were investigated using human liver microsomes. Previous studies showed PX-3 as the most potent CB1 and CB2 receptor agonist.

Half-life and clearance data were acquired using liquid chromatography- tandem mass spectrometry. Metabolite elucidation was performed using liquid chromatography high- resolution mass spectrometry in combination with Compound Discoverer®. A previously characterized SC, NM2201 was used as a control.

The calculated half-lives were 15.1±1.02, 3.4±0.27, 5.2±0.89 minutes for PX-1, PX-2, and PX-3 respectively. The calculated intrinsic clearance values were 0.046, 0.202, 0.133 mL/ min mg for PX-1, PX-2 and PX-3 respectively. Four metabolites of PX-1, six metabolites of PX-2 and five phase I metabolites of PX-3 were detected. Oxidative deamination was the common biotransformation between the three compounds. Elucidation of marker metabolites are useful to confirm consumption of SCs.

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