Improved Detection of Synthetic Cathinones ("Bath Salts")in Forensic Toxicology Samples

Synthetic cathinones are a new class of designer drug derived from khat (Catha edulis), a shrub native to the Horn of Africa and the Arabian peninsula. Chemically, they are phenethylamine derivatives with a ketone at the ß-carbon. Due to their amphetamine-like structure, the drugs can be classified as sympathomimetic amines. However, synthetic cathinones can produce a complex array of adrenergic and serotonergic effects, and the combination of stimulant and mood-altering sensations have contributed to the popularity of these substances among recreational drug users. Despite the federal government exercising its emergency scheduling authority late in 2011, manufacturers and distributors of synthetic cathinone products continue to circumvent regulation and enforcement efforts. According to a 2011 report from the National Drug Intelligence Center, drug users are attracted to these drugs because they are aware that they can evade most drug testing (NDIC, 2011). They further recognize that synthetic cathinone users who operate motor vehicles will likely go undetected. Analytical limitations for state and local forensic toxicology laboratories impact criminal and death investigation casework, and these deficiencies can have serious criminal justice consequences. The vast majority of forensic toxicology laboratories use GC/MS to identify drugs in biological evidence. This technique is widely used to identify synthetic cathinones in seized drugs (pills, powders, capsules). However, forensic toxicology investigations pose additional challenges because the pharmacologic properties of these drugs are still the topic of ongoing research and concentrations of the parent (unmetabolized) drug in biological samples require methods with additional sensitivity and specificity. A small number of scientific publications have addressed a limited number of synthetic cathinones in biological samples, but there have been no forensic toxicology reports to date that describe the simultaneous detection of the most prevalent synthetic cathinones. Chemical derivatization is usually necessary in order to increase specificity and improve chromatographic and spectroscopic properties of the drug. Analytical approaches to date have focused exclusively on acetylated derivatives for GC/MS analysis an approach that is widely used for other amphetamine-like drugs. However, not all synthetic cathinones, including important drugs like MDPV and naphyrone are capable of derivatization using this approach, and this seriously hampers identification in toxicology samples due to the limited spectroscopic specificity. We will develop new analytical methodology that is capable of identifying at least eight of the most prevalent synthetic cathinones in biological samples. These include mephedrone (4‐methylmethcathinone), 4-fluoromethcathinone (flephedrone), methylone (3,4-methylenedioxymethcathinone), butylone, ethylone, methedrone, 3,4-methylenedioxypyrovalerone (MDPV) and napthylprovalerone (naphyrone). We propose the investigation of new and existing derivatization reagents that are reactive towards the ketone group common to all cathinones. This universal approach allows all synthetic cathinones to be derivatized, improving sensitivity, specificity and overall assay performance. Once the preferred derivative has been identified and characterized, it will be used to develop an improved method for the detection of the eight target cathinones in biological samples. Solid phase extraction (SPE) and GC/MS will be used for isolation and identification purposes. The new procedure will undergo full scientific validation in collaboration with an ASCLD/LAB (American Society of Crime Laboratory Directors Laboratory Accreditation Board) accredited forensic laboratory. The new technique will be used to investigate the stability of the synthetic cathinones in biological samples, which will assist in the interpretation of results. ca/ncf