Mephedrone: a single-dose administration study to determine human pharmacokinetics after nasal insufflation and to detect mephedrone and its metabolit
Lead Research Organisation:
King's College London
Department Name: Analytical & Environmental Sciences
Abstract
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People |
ORCID iD |
| Mark Parkin (Primary Supervisor) | |
| Joanna Czerwinska (Student) |
Publications
Czerwinska J
(2019)
Stability of mephedrone and five of its phase I metabolites in human whole blood.
in Drug testing and analysis
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M014940/1 | 30/09/2015 | 29/09/2019 | |||
| 1721833 | Studentship | BB/M014940/1 | 30/09/2015 | 29/09/2019 | Joanna Czerwinska |
| Description | All analytes were detected in whole blood and plasma, where 4-CARBOXY reached the highest concentration. The mean Tmax of approximately 55 min for mephedrone corresponded well between whole blood and plasma, indicating rapid absorption of the drug after nasal insufflation. Other analytes had a more delayed Tmax but were all detected up to 6 h in both matrices, with mephedrone also being detectable on Day 2 in one participant in whole blood. Mephedrone had a mean half-life of 2.12 ± 0.33 h and 1.98 ± 0.30 h in whole blood and plasma, respectively. Moreover, chiral analysis revealed that R mephedrone reached higher concentrations than S mephedrone in whole blood and had comparable pharmacokinetic parameters to total mephedrone. It has been shown that the two enantiomers of mephedrone exhibit different pharmacokinetic profiles in humans, but the clinical significance of this finding is not yet fully understood. In urine, 4-CARBOXY and DHNM were the only metabolites detectable on Day 3, making them promising markers of mephedrone use. In the alternative biological matrices, mephedrone metabolites were detected for the first-time in head hair one month after mephedrone administration. Calculated NOR:mephedrone and DHNM:mephedrone ratios were 0.19 (n=1) and 0.21 (n=1), respectively. However, sample size was too small to suggest robust metabolite to mephedrone ratios that would differentiate external drug contamination from drug consumption. In fingerprint sweat, mephedrone and NOR were detected above the limit of detection in 62% and 3.8% of all samples, respectively. Inter- and intra-subject variability was observed which can be attributed to the differences in pressure applied during fingerprint deposition, the angle and duration of contact with the deposition surface coupled with an inability to control the 'amount' of collected sweat. Given these limitations fingerprint sweat may not be ideal for use in quantitative analysis until practical solutions to these problems are found. In dried blood spots, mephedrone, NOR and 4-CARBOXY were the only analytes detected in the majority of samples. Interestingly, capillary NOR concentrations were 2.42-fold and 1.58-fold higher than the concentrations measured in whole blood and plasma, respectively. In oral fluid, mephedrone and NOR were detected but their concentrations peaked earlier than in whole blood and plasma which may be due to the contamination of the oral cavity with mephedrone after nasal insufflation. |
| Exploitation Route | Low detectability of mephedrone and its metabolites in several biological matrices, such as fingerprint sweat and oral fluid, has been partially attributed to a single and relatively low dose of administered mephedrone. Future research would benefit from conducting a controlled mephedrone administration study with higher and/or repeated doses and larger sample size. The latter would also help minimise inter subject variability which was observed in the study. It has been shown that mephedrone enantiomers exhibit different pharmacokinetic profiles in humans which might be a result of pharmacokinetic processes occurring at different rates during drug absorption, distribution, metabolism or excretion. The mechanism responsible for the difference in concentrations has not been explored and warrants further work. In addition, clinical significance of this finding is not yet fully understood. The next useful step would be to conduct receptor binding assays. Even though mephedrone and its metabolites have been detected and quantified in samples collected from controlled administration studies, more translational research involving the analysis of clinical and forensic samples is needed. To my knowledge only one other study has reported the presence of mephedrone metabolites (DHM, NOR, HYDROXY and 4-CARBOXY) in urine and blood samples collected from road traffic cases. It is especially important to target NOR which has been shown to be an active metabolite able to cross the blood-brain barrier and contribute to the psychostimulant effects of mephedrone. Lastly, metabolites which have demonstrated longer windows of detection should be targeted in clinical and forensic studies where they could be used as markers of mephedrone use. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | Fingerprint sweat analysis by paper spray |
| Organisation | University of Surrey |
| Department | Department of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Fingerprint sweat samples were collected on triangular pieces of paper during this study. |
| Collaborator Contribution | Fingerprint sweat samples were sent to the University of Surrey for analysis. |
| Impact | Mephedrone and some of its metabolites were detected in some samples. |
| Start Year | 2018 |