The Low-Down on Methamphetamine Isomers: Prevalence and Pharmacology in Humans

According to the National Forensic Laboratory Information System (NFLIS)-Drug 2021 Annual Report, methamphetamine was the most frequently identified drug in federal, state, and local forensic laboratories. Methamphetamine exists as two stereoisomers: dextro-methamphetamine (D-MAMP) and levo-methamphetamine (L-MAMP). The D-MAMP stereoisomer is a central nervous system stimulant and drug of abuse, available in both pharmaceutical and clandestine preparations across the globe. As clandestine labs are rudimentary and uncontrolled, most street methamphetamine is a racemic mixture of D-MAMP and L-MAMP. The L-MAMP stereoisomer is also available over the counter (OTC) in nasal decongestants. However, most forensic laboratories (including seized drugs and toxicology) do not differentiate between isomers, assessing simply for methamphetamine. With advances in liquid chromatography technology and lowering costs, forensic laboratories are increasingly moving from GC-MS to LC-MS/MS techniques. With that shift, there is an opportunity to inform and empower toxicology and crime laboratories to separate and quantify methamphetamine and amphetamine enantiomers in casework. Separating methamphetamine enantiomers will maximize information gained from existing forensic evidence and workflows.

Alongside increasing prevalence in drug reports, 2021 results from the National Survey on Drug Use and Health (NSDUH) estimate that nearly one million Americans drove while under the influence of methamphetamine in the past year. Despite widespread methamphetamine use and abuse, translatable knowledge on the pharmacokinetics of both methamphetamine enantiomers across forensically relevant human biological matrices is lacking from the literature. Additionally, several metabolites (e.g., amphetamine and p-hydroxymethamphetamine) are psychoactive and may contribute to the impairment profile observed by law enforcement and other first responders. However, the stereoselectivity of methamphetamine metabolic pathways remains undefined, giving those who interpret toxicological testing results little to go on.

This project seeks to begin filling these knowledge gaps through a hybrid applied and foundational research project. Specifically, this work will have two major aims, (1) develop and validate an accessible methamphetamine enantiomer-specific identification and quantification method to maximize information gained from existing forensic evidence and (2) contribute to the fundamental scientific basis of knowledge surrounding methamphetamine pharmacology. Of note, the proposed work seeks to quantify methamphetamine enantiomer and metabolite concentrations in several human biological matrices following controlled study drug administration. We will also correlate analyte concentrations across plasma, whole blood, and oral fluid. Data gathered from this work will directly inform forensic science practice and translation of results to legal proceedings. CA/NCF