Development of an Enantioselective Method by Liquid Chromatography to Monitor 3,4-Methylenedioxypyrovalerone in Culture Media from Ecotoxicity Assays
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Standards
2.2. Materials and Equipments
2.3. Optimization of the Enantioseparation of MDPV
2.4. pH Stability Tests and Sample Preparation Procedure Optimization: Liquid-Phase Extraction and SPE
2.5. Method Application
3. Results and Discussion
3.1. Optimization of the Enantioseparation of MDPV
3.2. Sample Preparation Procedures’ Optimization: LPE and SPE
3.3. Enantioselective Method Application
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- UNODC. World Drug Report 2021, Booklet 2, Global Overview: Drug Demand, Drug Supply; United Nations Publication; United Nations: New York, NY, USA, 2021. [Google Scholar]
- Fitzgerald, N.D.; Cottler, L.B.; Palamar, J.J. Public health surveillance of new psychoactive substances: Recent developments. Curr. Opin. Psychiatry 2024, 37, 270–276. [Google Scholar] [CrossRef] [PubMed]
- Jurásek, B.; Čmelo, I.; Svoboda, J.; Čejka, J.; Svozil, D.; Kuchar, M. New psychoactive substances on dark web markets: From deal solicitation to forensic analysis of purchased substances. Drug Test. Anal. 2021, 13, 156–168. [Google Scholar] [CrossRef]
- UNODC. World Drug Report 2023, Booklet 3, Chapter 7, Use of the Dark Web and Social Media for Drug Supply; United Nations Publication; United Nations: New York, NY, USA, 2023. [Google Scholar]
- Boscolo-Berto, R. Challenges and future trends of forensic toxicology to keep a cut above the rest. Adv. Clin. Exp. Med. 2024, 33, 423–425. [Google Scholar] [CrossRef] [PubMed]
- EMCDDA. European Monitoring Centre for Drugs and Drug Addiction (2022), Risk Assessment Report on the New Psychoactive Substance 2-(Methylamino)-1-(3-Methylphenyl)Propan-1-One (3methylmethcathinone, 3-MMC) in Accordance with Article 5c of Regulation (EC) No 1920/2006 (as Amended), Risk Assessments; Publications Office of the European Union: Luxembourg, 2022. [Google Scholar]
- UNODC. World Drug Report 2023; United Nations Publication; United Nations: New York, NY, USA, 2023. [Google Scholar]
- UNODC. World Drug Report 2024; United Nations Publication; United Nations: New York, NY, USA, 2024. [Google Scholar]
- Oliver, C.F.; Palamar, J.J.; Salomone, A.; Simmons, S.J.; Philogene-Khalid, H.L.; Stokes-McCloskey, N.; Rawls, S.M. Synthetic cathinone adulteration of illegal drugs. Psychopharmacology 2019, 236, 869–879. [Google Scholar] [CrossRef]
- UNODC. World Drug Report 2023, Booklet 3, Chapter 8, Developments and Emerging Trends in Selected Drug Markets; United Nations Publication; United Nations: New York, NY, USA, 2023. [Google Scholar]
- UNODC. World Drug Report 2023, Booklet 3, Chapter 1, The Synthetic Drug Phenomenon; United Nations Publication; United Nations: New York, NY, USA, 2023. [Google Scholar]
- Daziani, G.; Lo Faro, A.F.; Montana, V.; Goteri, G.; Pesaresi, M.; Bambagiotti, G.; Montanari, E.; Giorgetti, R.; Montana, A. Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review. Int. J. Mol. Sci. 2023, 24, 6230. [Google Scholar] [CrossRef] [PubMed]
- Daswani, R.R.; Choles, C.M.; Kim, D.D.; Barr, A.M. A systematic review and meta-analysis of synthetic cathinone use and psychosis. Psychopharmacology 2024, 241, 875–896. [Google Scholar] [CrossRef]
- Chen, S.; Zhou, W.; Lai, M. Synthetic Cathinones: Epidemiology, Toxicity, Potential for Abuse, and Current Public Health Perspective. Brain Sci. 2024, 14, 334. [Google Scholar] [CrossRef]
- Soares, J.; Costa, V.M.; Bastos, M.L.; Carvalho, F.; Capela, J.P. An updated review on synthetic cathinones. Arch. Toxicol. 2021, 95, 2895–2940. [Google Scholar] [CrossRef]
- Pieprzyca, E.; Skowronek, R.; Nižnanský, L.; Czekaj, P. Synthetic cathinones—From natural plant stimulant to new drug of abuse. Eur. J. Pharmacol. 2020, 875, 173012. [Google Scholar] [CrossRef]
- EMCDDA. European Monitoring Centre for Drugs and Drug Addiction (2014), Report on the Risk Assessment of 1-(1,3-Benzodioxol-5-yl)-2-(Pyrrolidin-1-yl)Pentan-1-One (3,4-Methylenedioxypyrovalerone, MDPV) in the Framework of the Council Decision on New Psychoactive Substances, Risk Assessments; Publications Office of the European Union: Luxembourg, 2014. [Google Scholar]
- Baumann, M.H.; Bukhari, M.O.; Lehner, K.R.; Anizan, S.; Rice, K.C.; Concheiro, M.; Huestis, M.A. Neuropharmacology of 3,4-methylenedioxypyrovalerone (MDPV), its metabolites, and related analogs. Curr. Top. Behav. Neurosci. 2017, 32, 93–117. [Google Scholar] [CrossRef]
- Liveri, K.; Constantinou, M.A.; Afxentiou, M.; Kanari, P. A fatal intoxication related to MDPV and pentedrone combined with antipsychotic and antidepressant substances in Cyprus. Forensic Sci. Int. 2016, 265, 160–165. [Google Scholar] [CrossRef]
- La Maida, N.; Di Trana, A.; Giorgetti, R.; Tagliabracci, A.; Busardò, F.P.; Huestis, M.A. A review of synthetic cathinone–related fatalities from 2017 to 2020. Ther. Drug Monit. 2021, 43, 52–68. [Google Scholar] [CrossRef]
- Desharnais, B.; Daze, Y.; Huppertz, L.M.; Mireault, P.; Skinner, C.D. A case of fatal idiosyncratic reaction to the designer drug 3,4-methylenedioxypyrovalerone (MDPV) and review of the literature. Forensic Sci. Med. Pathol. 2017, 13, 350–354. [Google Scholar] [CrossRef] [PubMed]
- Kuczynska, K.; Bartkowska, K.; Djavadian, R.; Zwierzynska, E.; Wojcieszak, J. MDPV (3,4-methylenedioxypyrovalerone) administered to mice during development of the central nervous system produces persistent learning and memory impairments. Pharmacol. Rep. 2024, 76, 519–534. [Google Scholar] [CrossRef]
- Bade, R.; White, J.M.; Nguyen, L.; Tscharke, B.J.; Mueller, J.F.; O’Brien, J.W.; Thomas, K.V.; Gerber, C. Determining changes in new psychoactive substance use in Australia by wastewater analysis. Sci. Total Environ. 2020, 731, 139209. [Google Scholar] [CrossRef]
- Brandeburová, P.; Bodík, I.; Horáková, I.; Žabka, D.; Castiglioni, S.; Salgueiro-González, N.; Zuccato, E.; Špalkova, V.; Mackuľak, T. Wastewater-based epidemiology to assess the occurrence of new psychoactive substances and alcohol consumption in Slovakia. Ecotoxicol. Environ. Saf. 2020, 200, 110762. [Google Scholar] [CrossRef] [PubMed]
- Bade, R.; Bijlsma, L.; Sancho, J.V.; Baz-Lomba, J.A.; Castiglioni, S.; Castrignanò, E.; Causanilles, A.; Gracia-Lor, E.; Kasprzyk-Hordern, B.; Kinyua, J.; et al. Liquid chromatography-tandem mass spectrometry determination of synthetic cathinones and phenethylamines in influent wastewater of eight European cities. Chemosphere 2017, 168, 1032–1041. [Google Scholar] [CrossRef] [PubMed]
- Gao, T.; Du, P.; Xu, Z.; Li, X. Occurrence of new psychoactive substances in wastewater of major Chinese cities. Sci. Total Environ. 2017, 575, 963–969. [Google Scholar] [CrossRef]
- Castiglioni, S.; Salgueiro-González, N.; Bijlsma, L.; Celma, A.; Gracia-Lor, E.; Beldean-Galea, M.S.; Mackuľak, T.; Emke, E.; Heath, E.; Kasprzyk-Hordern, B.; et al. New psychoactive substances in several European populations assessed by wastewater-based epidemiology. Water Res. 2021, 195, 116983. [Google Scholar] [CrossRef]
- Aldubayyan, A.A.; Castrignanò, E.; Elliott, S.; Abbate, V. Development and validation of a chiral LC-MS/MS method for the separation and quantification of four synthetic cathinones in human whole blood and its application in stability analysis. Talanta 2023, 253, 123986. [Google Scholar] [CrossRef]
- Hambuchen, M.D.; Hendrickson, H.P.; Owens, S.M. Chiral determination of 3,4-methylenedioxypyrovalerone enantiomers in rat serum. Anal. Methods 2017, 9, 609–617. [Google Scholar] [CrossRef]
- Araújo, A.M.; Carvalho, M.; Costa, V.M.; Duarte, J.A.; Dinis-Oliveira, R.J.; Bastos, M.L.; Pinho, P.G.; Carvalho, F. In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV). Arch. Toxicol. 2021, 95, 509–527. [Google Scholar] [CrossRef] [PubMed]
- Langa, I.; Tiritan, M.E.; Silva, D.; Ribeiro, C. Gas chromatography multiresidue method for enantiomeric fraction determination of psychoactive substances in effluents and river surface waters. Chemosensors 2021, 9, 224. [Google Scholar] [CrossRef]
- Almeida, A.S.; Silva, B.; Pinho, P.G.; Remião, F.; Fernandes, C. Synthetic cathinones: Recent developments, enantioselectivity studies and enantioseparation methods. Molecules 2022, 27, 2057. [Google Scholar] [CrossRef]
- Suzuki, M.; Deschamps, J.R.; Jacobson, A.E.; Rice, K.C. Chiral resolution and absolute configuration of the enantiomers of the psychoactive “designer drug” 3,4-methylenedioxypyrovalerone. Chirality 2015, 27, 287–293. [Google Scholar] [CrossRef] [PubMed]
- Almeida, A.S.; Silva, B.; Silva, J.P.; Pereira, J.A.; Remiao, F.; Fernandes, C. Semi-preparative separation, absolute configuration, stereochemical stability and effects on human neuronal cells of MDPV enantiomers. Molecules 2023, 28, 2121. [Google Scholar] [CrossRef]
- Pérez-Pereira, A.; Carvalho, A.R.; Carrola, J.S.; Tiritan, M.E.; Ribeiro, C. Integrated approach for synthetic cathinone drug prioritization and risk assessment: In silico approach and sub-chronic studies in Daphnia magna and Tetrahymena thermophila. Molecules 2023, 28, 2899. [Google Scholar] [CrossRef]
- Costa, A.R.; Goncalves, V.M.F.; Castro, B.B.; Carrola, J.S.; Langa, I.; Pereira, A.; Carvalho, A.R.; Tiritan, M.E.; Ribeiro, C. Toxicity of the 3,4-methylenedioxymethamphetamine and its enantiomers to Daphnia magna after isolation by semipreparative chromatography. Molecules 2023, 28, 1457. [Google Scholar] [CrossRef]
- Danaceau, J.; Chambers, E.; Fountain, K. Analysis of “Bath Salt” Compounds from Urine for Forensic Toxicology Using μelution Mixed-Mode SPE Combined with UPLC/MS/MS Detection; Application Note; Waters: Milford, MA, USA, 2013. [Google Scholar]
- Lewin, A.H.; Seltzman, H.H.; Carroll, F.I.; Mascarella, S.W.; Reddy, P.A. Emergence and properties of spice and bath salts: A medicinal chemistry perspective. Life Sci. 2014, 97, 9–19. [Google Scholar] [CrossRef] [PubMed]
- Ciallella, H.L.; Rutter, L.R.; Nisbet, L.A.; Scott, K.S. Extended stability evaluation of selected cathinones. Front. Chem. 2020, 8, 597726. [Google Scholar] [CrossRef]
Sample | Cartridges | Cartridge Conditioning | Washing | Elution |
---|---|---|---|---|
Pre-acidified by adding concentrated H₂SO₄ | OASIS® MCX | MeOH (10 mL) and UPW (10 mL) | Mixture of 2.0% formic acid in water (2 mL) and MeOH (2 mL) | 5.0% NH4OH in ACN/IPA (60:40, v/v) (4 mL) |
OASIS® HLB | 2.0% formic acid in water (4 mL) | EtOH (4 mL) | ||
Pre-acidified by adding 4.0% H3PO4 in water | OASIS® MCX | MeOH (10 mL) and UPW (10 mL) | 2.0% formic acid in water (2 mL) and MeOH (2 mL) | 5.0% NH4OH in ACN/IPA (60:40, v/v) (4 mL) |
Mixture of 2.0% formic acid in water (2 mL) and MeOH (2 mL) | ||||
Pre-acidified by adding concentrated H₂SO₄ | Without | 2.0% formic acid in water (4 mL) | 5.0% NH4OH in EtOH (4 mL) | |
2.0% formic acid in water (2 mL) and MeOH (2 mL) | ||||
2.0% formic acid in water (3 mL) and MeOH (1 mL) | ||||
Mixture of 2.0% formic acid in water (2 mL) and MeOH (2 mL) |
Mobile Phase | Composition (v/v) | Flow Rate (mL min−1) | Injection Volume (μL) | MDPV (μg mL−1) | k′1 | k′2 | α | RS |
---|---|---|---|---|---|---|---|---|
0.1% DEA in Hex/EtOH | 97:3 | 0.5 | 20 | 100 | 0.62 | - | 1.00 | - |
99:1 | 0.5 | 20 | 100 | 1.62 | 1.93 | 1.19 | 0.74 | |
0.7 | 20 | 0.10 * | 1.03 | 1.30 | 1.26 | 3.42 | ||
0.05 ** | 1.04 | 1.29 | 1.24 | 2.98 | ||||
0.10 ** | 1.06 | 1.31 | 1.24 | 2.99 | ||||
30 | 0.05 ** | 1.04 | 1.28 | 1.23 | 3.25 | |||
40 | 0.05 ** | 1.03 | 1.27 | 1.24 | 3.21 | |||
0.10 ** | 1.07 | 1.35 | 1.27 | 3.66 | ||||
0.1% DEA in Hex/IPA | 99:1 | 0.7 | 40 | 1.0 ** | 2.19 | 2.89 | 1.32 | 7.96 |
98:2 | 0.3 | 40 | 1.0 ** | 1.95 | 2.45 | 1.26 | 4.85 | |
0.5 | 1.0 ** | 1.95 | 2.44 | 1.25 | 4.74 | |||
97:3 | 0.7 | 40 | 1.0 ** | - | - | - | - | |
0.5 | 1.0 ** | - | - | - | - | |||
0.3 | 1.0 ** | 1.50 | 1.80 | 1.20 | 4.37 |
CSP | Mobile Phase | Composition (v/v) | Flow Rate (mL min−1) | Injection Volume (μL) | Column Oven Temperature (°C) | MDPV (μg mL−1) | k′1 | k′2 | α | RS |
---|---|---|---|---|---|---|---|---|---|---|
Lux® 3 μm Cellulose-2 (150 × 4.6 mm I.D.) | 5 mM NH4OAc in UPW (pH 8.5)/EtOH | 50:50 | 0.7 | 40 | RT | 1.0 * | 1.44 | - | 1.00 | - |
5 mM NH4OAc in UPW (pH 8.5)/ACN | 50:50 | 0.7 | 40 | RT | 1.0 * | 1.36 | 1.44 | 1.05 | 0.50 | |
55:45 | 0.7 | 1.0 * | 2.87 | 3.01 | 1.05 | 0.89 | ||||
60:40 | 0.7 | 1.0 * | 1.67 | 1.79 | 1.07 | 1.12 | ||||
0.10 * | 1.66 | 1.79 | 1.07 | 1.16 | ||||||
65:35 | 0.7 | 0.10 * | 2.94 | 3.16 | 1.07 | 1.43 | ||||
0.10 ** | 2.90 | 3.11 | 1.07 | 1.42 | ||||||
0.8 | 0.10 * | 2.75 | 2.95 | 1.07 | 1.30 | |||||
1.0 | 0.10 * | 2.55 | 2.74 | 1.08 | 1.19 | |||||
70:30 | 0.8 | 0.50 * | 4.76 | 5.10 | 1.07 | 1.48 | ||||
1.0 | 0.50 * | 15.25 | 16.29 | 1.07 | 1.52 | |||||
5 mM NH4OAc in UPW (pH 8.7)/ACN | 74:26 | 1.0 | 40 | RT | 1.0 * | 32.31 | 34.97 | 1.08 | 2.08 | |
Lux® 3 μm Cellulose-2 (150 × 4.6 mm I.D.) | 5 mM NH4OAc in UPW/ACN (pH 8.5) | 70:30 | 0.3 | 10 | RT | 1.0 * | 9.03 | 9.71 | 1.08 | 1.19 |
35 | 1.0 * | 5.98 | 6.37 | 1.07 | 0.84 | |||||
20 mM NH4OAc in UPW/ACN (pH 8.5) | 70:30 | 0.3 | 10 | 35 | 1.0 * | 7.46 | 7.95 | 1.07 | 1.15 | |
5 | 25 | 0.10 * | 8.55 | 9.16 | 1.07 | 1.41 | ||||
30 | 1.0 * | 8.05 | 8.60 | 1.07 | 1.18 | |||||
35 | 0.10 * | 7.51 | 8.00 | 1.06 | 1.19 | |||||
20 mM NH4OAc in UPW/ACN (pH 8.5) | 75:25 | 0.3 | 5 | 25 | 1.0 * | 15.18 | 16.31 | 1.07 | 1.42 | |
30 | 1.0 * | 13.54 | 14.47 | 1.07 | 1.34 | |||||
35 | 1.0 * | 12.13 | 12.92 | 1.07 | 1.22 | |||||
CHIRALPAK® IF-3 (150 × 2.1 mm I.D.) | 5 mM NH4HCO3 in UPW (pH 8.8)/ACN | 10:90 | 0.3 | 5 | 30 | 1.0 # | 1.20 | 2.72 | 2.27 | 5.94 |
1.0 * | 1.31 | 2.92 | 2.23 | 8.76 | ||||||
5 mM NH4HCO3 in UPW (pH 8.8)/ACN | 10:90 | 0.3 | 5 | 30 | ||||||
1.0 * | 1.37 | 3.16 | 2.31 | 10.1 |
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Pérez-Pereira, A.; Gonçalves, V.M.F.; Ribeiro, A.R.L.; Fernandes, C.; Carrola, J.S.; Ribeiro, C.; Tiritan, M.E. Development of an Enantioselective Method by Liquid Chromatography to Monitor 3,4-Methylenedioxypyrovalerone in Culture Media from Ecotoxicity Assays. Separations 2024, 11, 248. https://doi.org/10.3390/separations11080248
Pérez-Pereira A, Gonçalves VMF, Ribeiro ARL, Fernandes C, Carrola JS, Ribeiro C, Tiritan ME. Development of an Enantioselective Method by Liquid Chromatography to Monitor 3,4-Methylenedioxypyrovalerone in Culture Media from Ecotoxicity Assays. Separations. 2024; 11(8):248. https://doi.org/10.3390/separations11080248
Chicago/Turabian StylePérez-Pereira, Ariana, Virgínia M. F. Gonçalves, Ana R. L. Ribeiro, Carla Fernandes, João S. Carrola, Cláudia Ribeiro, and Maria E. Tiritan. 2024. "Development of an Enantioselective Method by Liquid Chromatography to Monitor 3,4-Methylenedioxypyrovalerone in Culture Media from Ecotoxicity Assays" Separations 11, no. 8: 248. https://doi.org/10.3390/separations11080248