The significance of chirality of illicit drugs for the estimation of drugs abuse using the sewage epidemiology approach

Most illicit drugs are chiral compounds. Their enantiomers reveal different potency and are often characterised by stereoselective disposition in the body. Amphetamines for example are characterised by one asymmetric carbon centre and exist in the form of two enantiomers, which significantly differ in potency, e.g. S(+)-amphetamine has twice as high stimulant activity as R(-)-amphetamine. However, R(-)-amphetamine has been reported to be as effective as the S(+)-enantiomer in the development of the psychotic syndrome. The phenomenon of the chirality of amphetamine is crucial in forensic identification of its illicit use. This is because amphetamine has some limited therapeutic use in narcolepsy and attention deficit hyperactivity disorder. Amphetamine is also formed as a metabolite of methamphetamine and several prescription drugs such as selegiline.
The aim of this presentation is to raise awareness of the importance of the phenomenon of chirality in forensic estimation of drugs abuse via sewage epidemiology approach. The report will present results obtained during a ten month long monitoring programme of several WWTPs in the UK. To the authors’ knowledge this is the first report tackling the phenomenon of chirality in the estimation of drugs use using a sewage forensics approach. Among the studied chiral drugs are: amphetamine, methamphetamine, MDMA, MDEA, MDA, ephedrine and pseudoephedrine. The monitoring programme revealed that these chemicals are not released into wastewater in the form of racemic mixtures. It was for example observed that in the case of amphetamine, R(-)-enantiomer was dominant in all analysed wastewater samples. It was also noted that enantiomeric ratios of amphetamine enantiomers differed significantly between sampling points and sampling times and varied from 0.53 to 0.84. Similar patterns were observed in the case of other studied chiral drugs. There are several possible reasons for this behaviour. Among them are: (i) different metabolism patterns of enantiomers of the same drug with preferential metabolism of one enantiomer only, (ii) formation of illicit drugs as a result of metabolism of legally prescribed drugs, or (iii) use of drugs in non-racemic forms of drugs. Although a complex and demanding process, the verification of enantiomeric ratios can provide vital information about patterns of drugs usage and can help in the differentiation between their legal and illicit usage.