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1.
Environ Sci Pollut Res Int ; 27(8): 8157-8165, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31900768

RESUMO

Methamphetamine has become one of the most widely used illicit drugs in China. To understand the current situation in China, the prevalence and consumption of methamphetamine were estimated through wastewater-based epidemiology (WBE) in the present study. Methamphetamine concentrations ranged from 42.6 ng/L (Harbin) to 700 ng/L (Xi'an) in influent wastewater samples collected from 27 wastewater treatment plants (WWTPs) in 22 Chinese cities. The estimated consumption of methamphetamine was 23.0 (Dingxi) to 376 (Xi'an) mg/day/1000 inhabitants with a mean value of 157 mg/day/1000 inhabitants. The annual consumption in 2018 was estimated to be 84 tons (95% confidence interval, 44-136), which was 26% lower than that in 2014. The prevalence of methamphetamine use was 0.64% (95% confidence interval, 0.18-1.25), indicating that more than five million people used methamphetamine in 2018. Although drug abuse is common in the country, the consumption showed a different spatial pattern, with the highest values in Central China and the lowest use in Northeast China, so drug use is still considered a geographic and culture-dependent behaviour. The results indicated that WBE can not only be used to assess the trends of illicit drug use, but also to analyse the spatial differences in the whole country, which will provide complementary evidence for the prevention and control of methamphetamine use.


Assuntos
Metanfetamina , Poluentes Químicos da Água , China , Cidades , Metanfetamina/análise , Metanfetamina/química , Vigilância Epidemiológica Baseada em Águas Residuárias
2.
Artigo em Inglês | MEDLINE | ID: mdl-31374422

RESUMO

Currently, consumption of illicit drugs and pharmaceuticals has increased significantly. Many of these substances are chiral and can be available as racemates or enantiomerically pure. Determination of the enantiomeric fraction (EF) in wastewater is useful for: i) distinguishing between the consumption of prescribed and illicit drugs; ii) identification of possible local of illegal synthesis; iii) illegal discharge of sewage and estimation of illicit drugs and pharmaceuticals consumption by a community (wastewater-based epidemiology). This work describes the development of an indirect method by gas chromatography-mass spectrometry (GC-MS) for enantiomeric quantification of chiral substances namely psychoactive drugs and ß-blockers based on the formation of diastereomers using (R)-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride ((R)-MTPA-Cl) as chiral derivatization reagent. The developed method presented linearity (R2 > 0.99) for 20 compounds, 9 diastereomer pairs and paroxetine (PAR) and sertraline (SER). Recovery ranged from 80.7 to 114.5% (RSD < 9.1%) and accuracy between 84.6 and 118% (RSD < 9.9%). The limits of detection (LOD) varied from 0.03 and 26.0 ngL-1 and limits of quantification (LOQ) from 0.15 and 104 ngL-1. Results showed the occurrence of amphetamine (AMP), illicit drugs as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MAMP), alprenolol (ALP), norfluoxetine (NFLX), (SER), metoprolol (MET) and propranolol (PHO) at concentrations ranging from 21.7 ngL-1 (MDMA) to 622 ngL-1 (PHO). Measured concentrations were used to estimate the drug loads of the target chiral substances in a specific population. The EF was determined providing valuable information about the consumption and origin of the target drugs.


Assuntos
Antagonistas Adrenérgicos beta/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Psicotrópicos/química , Antagonistas Adrenérgicos beta/isolamento & purificação , Anfetamina/química , Anfetamina/isolamento & purificação , Limite de Detecção , Metanfetamina/química , Metanfetamina/isolamento & purificação , Psicotrópicos/isolamento & purificação , Esgotos/química , Estereoisomerismo , Águas Residuárias/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação
3.
Fa Yi Xue Za Zhi ; 35(3): 337-343, 2019 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31282632

RESUMO

Abstract: Methamphetamine (MAMP) is a kind of amphetamine-type stimulants (ATS) which contains one chiral carbon atom in its structure. Therefore a pair of enantiomers, S-(+)-MAMP and R-(-)-MAMP exist. R type and S type methamphetamines possess similar physicochemical properties, but has largely different pharmacological and toxic effects. S-(+)-MAMP is the main component of addictive drug "Ice" at present, seriously affecting human health and public safety. The separation analysis and mechanism of toxic effects discussions on MAMP are the current research focuses. This paper reviews the research progress of separation analysis methods and toxic effects of methamphetamine enantiomers to provide reference for forensic study and forensic practice.


Assuntos
Metanfetamina/química , Estimulantes do Sistema Nervoso Central , Humanos , Estereoisomerismo , Detecção do Abuso de Substâncias
4.
Molecules ; 24(13)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31323938

RESUMO

Sample preparation is an important step in the isolation of target compounds from complex matrices to perform their reliable and accurate analysis. Hair samples are commonly pulverized or processed as fine cut, depending on preference, before extraction by techniques such as solid-phase extraction (SPE), liquid-liquid extraction, and other methods. In this study, a method based on hybrid solid-phase extraction (hybridSPE) and gas chromatography-mass spectrometry (GC-MS) was developed and validated for the determination of methamphetamine (MA) and amphetamine (AP) in hair. The hair samples were mechanically pulverized after washing with de-ionized water and acetone. The samples were then sonicated in methanol at 50 °C for 1 h and centrifuged at 50,000× g for 3 min. The supernatants were transferred onto the hybridSPE cartridge and extracted using 1 mL of 0.05 M methanolic hydrogen chloride. The combined solutions were evaporated to dryness, derivatized using pentafluoropropionic anhydride, and analyzed by GC-MS. Excellent linearity (R2 > 0.9998) was achieved in the ranges of 0.05-5.0 ng/mg for AP and 0.1-10.0 ng/mg for MA. The recovery was 83.4-96.8%. The intra- and inter-day accuracies were -9.4% to 5.5% and -5.1% to 3.1%, while the intra- and inter-day precisions were within 8.3% and 6.7%, respectively. The limits of detections were 0.016 ng/mg for AP and 0.031 ng/mg for MA. The validated hybridSPE method was applied to dyed hair for MA and AP extraction and compared to a methanol extraction method currently being used in our laboratory. The results showed that an additional hybridSPE step improved the recovery by 5.7% for low-concentration quality control (QC) samples and by 24.1% for high-concentration QC samples. Additionally, the hybridSPE method was compared to polymeric reversed-phase SPE methods, and the absolute recoveries for hybridSPE were 50% and 20% greater for AP (1.5 ng/mg) and MA (3.0 ng/mg), respectively. In short, the hybridSPE technique was shown to minimize the matrix effects, improving GC-MS analysis of hair. Based on the results, the proposed method proved to be effective for the selective determination of MA and AP in hair samples.


Assuntos
Anfetamina/química , Anfetamina/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Cabelo/química , Metanfetamina/química , Metanfetamina/isolamento & purificação , Extração em Fase Sólida , Humanos , Reprodutibilidade dos Testes
5.
J Sep Sci ; 42(17): 2796-2804, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222942

RESUMO

A method for the preparation of novel mixed-mode reversed-phase/strong cation exchange stationary phase for the separation of fixed-dose combination drugs has been developed. An epoxysilane bonded silica prepared by vapor phase deposition was used as a starting material to produce diol, octadecyl, sulfonate, and mixed octadecyl/sulfonate groups bonded silica phases. The chemical structure and surface coverage of the functional groups on these synthesized phases were confirmed by fourier-transform infrared and solid-state 13 C NMR spectroscopy and elemental analysis. Alkylbenzene homologs, basic drugs, nucleobases and alkylaniline homologs were used as probes to demonstrate the reversed-phase, ion exchange, hydrophilic interaction and mixed-mode retention behaviors of these stationary phases. The octadecyl/sulfonate bonded silica exhibits pronounced mixed-mode retention behavior and superior retentivity and selectivity for alkylaniline homologs. The mixed-mode retention is affected by either ionic or solvent strength in the mobile phase, permiting optimization of a separation by fine tuning these parameters. The mixed-mode stationary phase was applied to separate two fixed-dose combination drugs: compound reserpine tablets and compound methoxyphenamine capsules. The results show that simultaneous separation of multiple substances in the compound dosage can be achieved on the mixed-mode phase, which makes multi-cycles of analysis for multiple components obsolete.


Assuntos
Compostos de Epóxi/química , Metanfetamina/análogos & derivados , Reserpina/isolamento & purificação , Cápsulas/química , Cápsulas/isolamento & purificação , Cromatografia de Fase Reversa , Metanfetamina/química , Metanfetamina/isolamento & purificação , Estrutura Molecular , Reserpina/química , Dióxido de Silício/química , Comprimidos/química , Comprimidos/isolamento & purificação
6.
Rapid Commun Mass Spectrom ; 33(11): 995-1005, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30849207

RESUMO

RATIONALE: We investigated whether chemical information on the origin of ephedrine and pseudoephedrine (ephedrines) can be acquired by liquid chromatography/mass spectrometry (LC/MS) as a substitute method for stable isotope ratio mass spectrometry (IRMS), which is not routinely available in forensic laboratories. We examined the characteristic inorganic elemental contaminants of ephedrines as a preliminary study. METHODS: The stable isotope ratios measured by IRMS analysis are expressed relative to the stable isotope ratios of conventional standards. Referring to the method using validated standard samples in IRMS, we selected a standard sample for acquiring stable isotopic ratio by LC/MS. The abundance ratio of the [M + 2H]+ ion to the [M + H]+ ion was measured by means of selected ion monitoring. We carried out qualitative analysis of inorganic elements contained in ephedrines produced by different manufacturing methods with ICPMS. RESULTS: We found that the ratio of stable isotope ion to molecular ion (stable isotope ratio) of ephedrines could be measured with LC/MS. The stable isotope ratio of ephedrines determined by LC/MS were confirmed to show relatively good correlations with the carbon and hydrogen stable isotope ratios found by IR-MS. We identified strontium as a characteristic inorganic element contained in ephedrines prepared by the semisynthetic method from molasses, or in the biosynthetic method from ephedra plants. CONCLUSIONS: Our results suggest that useful chemical information can be obtained by LC/MS, which is easy to carry out, and is generally available in forensic laboratories. It would be worthwhile to investigate the usefulness of stable isotope ratio measurements of Sr in the future.


Assuntos
Cromatografia Líquida/métodos , Efedrina/química , Metanfetamina/química , Espectrometria de Massas em Tandem/métodos
7.
Chem Biol Interact ; 305: 134-147, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30922767

RESUMO

Methiopropamine (MPA) is structurally categorized as a thiophene ring-based methamphetamine (MA) derivative. Although abusive potential of MPA was recognized, little is known about the neurotoxic potential of MPA up to now. We investigated whether MPA induces dopaminergic neurotoxicity, and whether MPA activates a specific dopamine receptor. Here, we observed that treatment with MPA resulted in dopaminergic neurotoxicity in a dose-dependent manner. MPA treatment potentiated oxidative parameters (i.e., increases in the level of reactive oxygen species, 4-hydroxynonenal, and protein carbonyl), M1 phenotype-related microglial activity, and pro-apoptotic property (i.e., increases in Bax- and cleaved caspase-3-expressions, while a decrease in Bcl-2-expression). Moreover, treatment with MPA resulted in significant impairments in dopaminergic parameters [i.e., changes in dopamine level, dopamine turnover rate, tyrosine hydroxylase (TH) levels, dopamine transporter (DAT) expression, and vesicular monoamine transporter-2 (VMAT-2) expression], and in behavioral deficits. Both dopamine D1 receptor antagonist SCH23390 and D2 receptor antagonist sulpiride protected from these neurotoxic consequences. Therefore, our results suggest that dopamine D1 and D2 receptors simultaneously mediate MPA-induced dopaminergic neurodegeneration in mice via oxidative burdens, microgliosis, and pro-apoptosis.


Assuntos
Metanfetamina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Benzazepinas/farmacologia , Benzazepinas/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Antagonistas dos Receptores de Dopamina D2/farmacologia , Antagonistas dos Receptores de Dopamina D2/uso terapêutico , Febre/prevenção & controle , Locomoção/efeitos dos fármacos , Masculino , Metanfetamina/síntese química , Metanfetamina/química , Camundongos , Camundongos Endogâmicos ICR , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Dopamina D2/química , Sulpirida/farmacologia , Sulpirida/uso terapêutico , Tirosina 3-Mono-Oxigenase/metabolismo
8.
Psychopharmacology (Berl) ; 236(3): 953-962, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30345459

RESUMO

RATIONALE: Synthetic cathinones continue to emerge in recreational drug markets worldwide. 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone) and 1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone) are derivatives of the cathinone compound, 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (methylone), that are being detected in drug products and human casework. OBJECTIVES: The purpose of the present study was to examine the neuropharmacology of butylone and pentylone using in vitro and in vivo methods. METHODS: In vitro uptake and release assays were carried out in rat brain synaptosomes and in cells expressing human dopamine transporters (DAT) and 5-HT transporters (SERT). In vivo microdialysis was performed in the nucleus accumbens of conscious rats to assess drug-induced changes in neurochemistry. RESULTS: Butylone and pentylone were efficacious uptake blockers at DAT and SERT, though pentylone was more DAT-selective. Both drugs acted as transporter substrates that evoked release of [3H]5-HT at SERT, while neither evoked release at DAT. Consistent with the release data, butylone and pentylone induced substrate-associated inward currents at SERT but not DAT. Administration of butylone or pentylone to rats (1 and 3 mg/kg, i.v.) increased extracellular monoamines and motor activity, but pentylone had weaker effects on 5-HT and stronger effects on motor stimulation. CONCLUSIONS: Our data demonstrate that increasing the α-carbon chain length of methylone creates "hybrid" transporter compounds which act as DAT blockers but SERT substrates. Nevertheless, butylone and pentylone elevate extracellular dopamine and stimulate motor activity, suggesting both drugs possess significant risk for abuse.


Assuntos
Alcaloides/farmacologia , Anfetaminas/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Antagonistas de Dopamina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Medicamentos Sintéticos/farmacologia , 3,4-Metilenodioxianfetamina/análogos & derivados , 3,4-Metilenodioxianfetamina/química , 3,4-Metilenodioxianfetamina/farmacologia , Alcaloides/química , Anfetaminas/química , Animais , Estimulantes do Sistema Nervoso Central/química , Antagonistas de Dopamina/química , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Masculino , Metanfetamina/análogos & derivados , Metanfetamina/química , Metanfetamina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ratos , Ratos Sprague-Dawley , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Medicamentos Sintéticos/química
9.
Psychopharmacology (Berl) ; 236(3): 881-890, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30069588

RESUMO

RATIONALE: The synthetic cathinones are a class of designer drugs of abuse that share a common core scaffold. The pharmacokinetic profiles of the synthetic cathinones vary based on the substitutions to the core scaffold. OBJECTIVES: To provide a summary of the literature regarding the pharmacokinetic characteristics of the synthetic cathinones, with a focus on the impact of the structural modifications to the pharmacokinetics. RESULTS: In many, but not all, instances the pharmacokinetic characteristics of the synthetic cathinones can be reasonably predicted based on the substitutions to the core scaffold. Mephedrone and methylone are chemically alike and have similar Tmax and t1/2 in male rats. MDPV, a structurally distinct synthetic cathinone from mephedrone and methylone, has a lower Tmax and t1/2. Increasing the length of the alkyl chain on the α position of methylone, to produce pentylone, results in increased plasma concentrations and longer t1/2. Metabolism of the synthetic cathinones is reasonably predictable based on the chemical structure, and several phase I metabolites retain pharmacodynamic activity. CYP2D6 is implicated in the metabolism of all of the synthetic cathinones, and other P450s (CYP1A2, CYP2B6, and CYP2C19) are known to contribute variably to the metabolism of specific synthetic cathinones. CONCLUSIONS: Continued research will lead to a better understanding of the pharmacokinetic changes associated with structural modifications to the cathinone scaffold, and potentially in the long range, enhanced overdose and addiction therapy. Additionally, the areas of polydrug use and pharmacogenetics have been largely overlooked with regard to synthetic cathinones.


Assuntos
Alcaloides/química , Alcaloides/farmacocinética , Medicamentos Sintéticos/química , Medicamentos Sintéticos/farmacocinética , Alcaloides/efeitos adversos , Anfetaminas/efeitos adversos , Anfetaminas/química , Anfetaminas/farmacocinética , Animais , Drogas Desenhadas/efeitos adversos , Drogas Desenhadas/química , Drogas Desenhadas/farmacocinética , Humanos , Metanfetamina/efeitos adversos , Metanfetamina/análogos & derivados , Metanfetamina/química , Metanfetamina/farmacocinética , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Medicamentos Sintéticos/efeitos adversos
10.
Forensic Sci Int ; 295: 54-63, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572220

RESUMO

3-Methylmethcathinone (3-MMC or metaphedrone) is a synthetic cathinone, recently introduced in the market of the new psychoactive substances (NPS), initially to replace mephedrone (4-methylmethcathinone or 4-MMC), and rapidly widespread among drug users. 3-Methylmethcathinone is legally controlled in many countries, but is still easily available for purchase from websites, and frequently found in recreational settings. Most toxicological data on this drug come from human case reports of intoxications. Thus, further investigation on their pharmacological and toxicological properties is necessary to evaluate its potential harmful effects. The present work provides a review on the available data about 3-MMC legal status, chemistry, patterns of use, prevalence, biological effects, toxicokinetics, toxicity and factors affecting stimulant/toxicological effects.


Assuntos
Metanfetamina/análogos & derivados , Psicotrópicos/farmacologia , Psicotrópicos/envenenamento , Transtornos Relacionados ao Uso de Anfetaminas/sangue , Interações Medicamentosas , Humanos , /farmacologia , Metanfetamina/química , Metanfetamina/farmacologia , Metanfetamina/envenenamento , Estrutura Molecular , Psicotrópicos/química , Medicamentos Sintéticos/química , Medicamentos Sintéticos/farmacologia , Medicamentos Sintéticos/envenenamento , Temperatura , Distribuição Tecidual
11.
Int J Legal Med ; 133(2): 467-473, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30564915

RESUMO

The differentiation between single methamphetamine consumption and co-consumption with amphetamine is difficult, however possible by enantioselective analysis due to different preferred synthesis pathways of both substances. We quantified (R)-(-) and (S)-(+)-enantiomers of methamphetamine and amphetamine by a fast liquid chromatographic tandem-mass spectrometric method using a Lux® 3-µm AMP 150 × 3.0 mm analytical column after simple protein precipitation with methanol. Method validation for quantitative detection showed limits of quantification < 5 ng/mL, linearity in a range between 5 and 300 ng/mL and bias and imprecision data < 15%. Overall, 134 plasma samples of police cases from the German regions of Franconia and Northrhine-Westphalia were analyzed for the enantiomers of methamphetamine and amphetamine. In 28 cases, the intake of racemic illicit amphetamine could be demonstrated; (R)-(-) / (S)-(+)-amphetamine concentration ratios in these cases were between 1.38 and 4.50 with most of the ratios being < 2.0. These ratios were compared to a subgroup of 25 consumers with a co-consumption of (S)-(+)-methamphetamine and racemic amphetamine detected by the qualitative proof of (R)-(-)-amphetamine but also by (R)-(-) / (S)-(+)-amphetamine concentration ratios (< 1 in 11 of 25 cases). Within our collective of 106 plasma samples after methamphetamine use, 25 samples showed co-consumption with amphetamine which shows that co-consumption of both stimulants is not a rare scenario. Furthermore, we could show that if non-stereoselective methods are used and the concentration ratio of total methamphetamine/total amphetamine is determined, a reliable estimation of co-consumption is not possible.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Anfetamina/química , Estimulantes do Sistema Nervoso Central/química , Metanfetamina/química , Anfetamina/sangue , Estimulantes do Sistema Nervoso Central/sangue , Cromatografia Líquida , Humanos , Metanfetamina/sangue , Estereoisomerismo , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem
12.
Psychopharmacology (Berl) ; 236(3): 973-988, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30448989

RESUMO

BACKGROUND: The appearance of stimulant-class new psychoactive substances (NPS) is a frequent and significant problem in our society. Cathinone variants are often sold illegally as 3,4-methylenedioxy methamphetamine ("ecstasy") or disguised for legal sale using misleading names such as "bath salts" and carry the risk of promoting disruptive mental states, addiction, and fatal overdose. The principal targets of these recreational drugs are monoamine transporters expressed in catecholaminergic and serotonergic neurons. Some transporter ligands can be transported into cells, where they can promote a massive release of neurotransmitters through reverse transport, and others can block uptake. A ligand's dopamine vs. serotonin transporter selectivity, potency, and activity as a substrate or blocker can help elucidate the abuse liability and subjective effects of a drug. OBJECTIVES: Here, we describe the discovery, development, and validation of an emerging methodology for compound activity assessment at monoamine transporters. KEY FINDINGS: Substrates generate inward electrical currents through transporters and can depolarize the plasma membrane, whereas blockers work as a "cork in a bottle" and function as antagonists. Voltage-gated Ca2+ channels were co-expressed with monoamine transporters in cultured cells and used to measure fluctuations of the membrane electrical potential. In this system, substrates of monoamine transporters produce reliable dose-dependent Ca2+ signals, while blockers hinder them. DISCUSSION: This system constitutes a novel use of voltage-gated Ca2+ channels as biosensors for the purpose of characterizing ligand activity at monoamine transporters using fluorimetry. This approach in combination with in vivo evaluations of drugs' abuse-related effects is a powerful strategy for anticipating potential stimulant-class NPS.


Assuntos
Alcaloides/análise , Anfetaminas/análise , Bioengenharia/métodos , Técnicas Biossensoriais/métodos , Canais de Cálcio/análise , Psicotrópicos/análise , Alcaloides/química , Anfetaminas/química , Animais , Bioengenharia/tendências , Técnicas Biossensoriais/tendências , Canais de Cálcio/química , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Humanos , /química , Metanfetamina/análise , Metanfetamina/química , Psicotrópicos/química , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
13.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1100-1101: 158-164, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30336346

RESUMO

The enantioresolution of pentedrone and methylone was carried out at a multi-milligram scale by liquid chromatography on a Chiralpak AS® stationary phase. The excellent enantioresolution using this column allowed to collect highly pure enantiomeric fractions, achieving enantiomeric ratios higher than 98%. An overall recovery of 72% was achieved for pentedrone enantiomers and 80% for methylone. Furthermore, the absolute configuration of the enantiomers of both cathinones was determined for the first time by electronic circular dichroism (ECD) spectroscopy, with the aid of theoretical calculations, as (+)­(S) and (-)­(R)-pentedrone, and (-)­(S) and (+)­(R)­methylone.


Assuntos
Metanfetamina/análogos & derivados , Metilaminas/análise , Metilaminas/química , Pentanonas/análise , Pentanonas/química , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Metanfetamina/análise , Metanfetamina/química , Modelos Moleculares , Estereoisomerismo
14.
J Sep Sci ; 41(23): 4281-4285, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30267460

RESUMO

A liquid chromatographic chiral stationary phase, which contains two N-CH3 amide connecting groups, based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid was first applied to the resolution of methoxyphenamine (2-methoxy-N-methylamphetamine, a ß-adrenergic receptor agonist used as a bronchodilator). The resolution of methoxyphenamine on the chiral stationary phase containing two N-CH3 amide connecting groups was quite successful with the separation factor (α) of 1.42 and resolution (RS ) of 4.22 compared with those (α of 1.09 and RS of 1.55) on the chiral stationary phase containing two N-H amide connecting groups. In addition, the chiral stationary phase containing two N-CH3 amide connecting groups was applied to the resolution of methoxyphenamine analogues. From the comparison of the resolution results of methoxyphenamine with those of methoxyphenamine analogues on the chiral stationary phase containing two N-CH3 amide connecting groups, the N-methyl group and the 2-methoxyphenyl group of methoxyphenamine were elucidated to be the structurally essential parts for the resolution on the chiral stationary phase.


Assuntos
Éteres de Coroa/química , Metanfetamina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Metanfetamina/química , Metanfetamina/isolamento & purificação , Estrutura Molecular
15.
J Colloid Interface Sci ; 531: 654-663, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071490

RESUMO

In the present study, a sulfonic acid functionalized enantio-selective resinous material was developed for effective chiral separation of (±)-methamphetamine racemate. R-methamphetamine-sulfonamide phenolic derivative was first prepared and fully characterized utilizing instrumental and spectroscopic techniques, then the sulfonamide was implemented in an acid catalyzed condensation copolymerization with phenol and formaldehyde. The resulted resinous material was then exposed to successive alkaline and acidic treatments in order to remove the R-methamphetamine enantiomer out of the resin matrix and obtaining the molecularly imprinted enantio-selective material, which was also investigated by scanning electron microscope, FTIR and XPS spectroscopy. The maximum selective extraction of the R-methamphetamine enantiomer was achieved at pH 7. The adsorption isotherms indicated an adsorption capacity of 233 ±â€¯1 mg/g and followed the well-known Langmuir model. Also, the enantio-separation experiment of the racemic mixture was performed by column technique and both the supernatant loading and the eluant recovery solutions indicated an enantiomeric excess of 80% and 67% related to S- and R-methamphetamine, respectively.


Assuntos
Estimulantes do Sistema Nervoso Central/isolamento & purificação , Metanfetamina/isolamento & purificação , Impressão Molecular/métodos , Resinas Sintéticas/química , Ácidos Sulfônicos/química , Adsorção , Estimulantes do Sistema Nervoso Central/química , Metanfetamina/química , Modelos Moleculares , Estereoisomerismo
16.
Electrophoresis ; 39(19): 2406-2409, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29998474

RESUMO

Methcathinone (ephedrone), 4-methylmethcathinone (mephedrone), and 3-methylmethcathinone (metaphedrone) are toxicologically-important cathinone derivatives used commonly as designer drugs. In this work we show the first method allowing to separate simultaneously all these molecules in a chiral medium, ensuring good resolution between all enantiomers. Eight cyclodextrins have been tested as potential chiral selectors, the best results were obtained with 2-hydroxyethyl-ß-cyclodextrin, unreported so far for efficient separation of cathinones. After optimization, the method was calibrated and validated with and without the use of internal standard. The addition of standard improved an overall repeatability and precision, the use of electrophoretic mobility ratio was especially favorable (RSD < 1%). It was demonstrated that the method may be easily extended by introducing the additional cathinone-related drugs to the sample, maintaining satisfactory separation efficiency.


Assuntos
Eletroforese Capilar/métodos , Metanfetamina/análogos & derivados , Propiofenonas/isolamento & purificação , beta-Ciclodextrinas/química , Limite de Detecção , Modelos Lineares , Metanfetamina/análise , Metanfetamina/química , Metanfetamina/isolamento & purificação , Propiofenonas/análise , Propiofenonas/química , Reprodutibilidade dos Testes , Estereoisomerismo
17.
Forensic Sci Int ; 290: 162-168, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30053735

RESUMO

Rapid and nondestructive near infrared spectroscopy (NIR) methods have been developed for simultaneous qualitative and quantitative analysis of methamphetamine, ketamine, heroin, and cocaine in seized samples. This is the first systematic report regarding a qualitative and quantitative procedure of applying NIR for drug analysis. A total of 282 calibration samples and 836 prediction samples were used for the building and validating of qualitative and quantitative models. Two qualitative analysis modeling methods for soft independent modeling by class analogy (SIMCA) and supporting vector machine (SVM) were compared. From its excellent performance in rejecting false positive results, SIMCA was chosen. The drug concentrations in the calibration and validation sample sets were analyzed using high-performance liquid chromatography. Based on the use of first-order derivative spectral data after standard normal variate (SNV) transformation correction, in the wavelength range from 10,000 to 4000cm-1, four partial least squares quantitative-analysis models were built. The coefficients of determination for all calibration models were >99.3, and the RMSEC, RMSECV, and RMSEP were all less than 1.6, 2.9, and 3.6%, respectively. The results obtained here indicated that NIR with chemometric methods was accurate for qualitative and quantitative analysis of drug samples. This methodology provided a potentially useful alternative to time-consuming gas chromatography-mass spectroscopy and high-performance liquid chromatography methods.


Assuntos
Cocaína/química , Heroína/química , Ketamina/química , Metanfetamina/química , Entorpecentes/química , Cromatografia Líquida de Alta Pressão , Toxicologia Forense/métodos , Análise dos Mínimos Quadrados , Análise de Componente Principal , Espectroscopia de Luz Próxima ao Infravermelho
18.
Sci Total Environ ; 643: 827-834, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29958170

RESUMO

Enantiomeric profiling was used in this study to investigate the consumption of amphetamine and methamphetamine in regional and urban Southeast Queensland, Australia over a period of seven years. S(+) methamphetamine was predominantly consumed in both urban and regional areas, showing a two and three fold increase in urban and regional catchments respectively between 2011 and 2017. The ratio of amphetamine to methamphetamine (AMP/METH) in wastewater reflected the expected excretion profile of methamphetamine consumption indicating the presence of amphetamine in this study was primarily the result of methamphetamine metabolism. However, the occasional occurrence of R(-) amphetamine in samples containing higher AMP/METH ratios, suggested the consumption of racemic amphetamine. The R(-) methamphetamine enantiomer was also identified in several samples, possibly indicative that the phenyl-2-propanone (P2P) synthesis process rather than the more typical reduction of ephedrines was also being used to manufacture methamphetamine. Furthermore, we identified two samples with a significantly different enantiomer ratio for the METH and AMP as well as a much lower AMP/METH concentration ratio suggesting contribution from direct disposal of methamphetamine into the sewer. This study demonstrated that enantiomeric profiling in wastewater-based epidemiology can provide valuable information for evaluating the origin of amphetamine in wastewater as either a metabolite of methamphetamine consumption or amphetamine itself.


Assuntos
Anfetamina/química , Monitoramento Ambiental , Metanfetamina/química , Águas Residuárias/química , Poluentes Químicos da Água/química , Anfetamina/análise , Austrália , Metanfetamina/análise , Queensland , Detecção do Abuso de Substâncias/métodos , Poluentes Químicos da Água/análise
19.
ACS Chem Neurosci ; 9(10): 2379-2394, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-29714473

RESUMO

Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These "synthetic cathinones" include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. This Review will thus detail (i) historical context of cathinone use and the rise of "dark" synthetic derivatives, (ii) structural features and mechanisms of synthetic cathinones, (iii) behavioral effects observed clinically and in animals under controlled laboratory conditions, and (iv) neurotransmitters and circuits that may be targeted to manage synthetic cathinone abuse in humans.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/farmacologia , Alcaloides/história , Animais , Comportamento Animal/efeitos dos fármacos , Benzodioxóis/química , Benzodioxóis/história , Benzodioxóis/farmacologia , Temperatura Corporal/efeitos dos fármacos , Catha/química , Estimulantes do Sistema Nervoso Central/história , Dopamina/metabolismo , História do Século XXI , História Medieval , Humanos , Locomoção/efeitos dos fármacos , Metanfetamina/análogos & derivados , Metanfetamina/química , Metanfetamina/história , Metanfetamina/farmacologia , Pirrolidinas/química , Pirrolidinas/história , Pirrolidinas/farmacologia , Serotonina/metabolismo , Transtornos Relacionados ao Uso de Substâncias , Transmissão Sináptica/efeitos dos fármacos
20.
ACS Chem Neurosci ; 9(7): 1829-1839, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29697951

RESUMO

4-Methylamphetamine (4-MA) is an emerging drug of abuse that acts as a substrate at plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), thereby causing nonexocytotic release of monoamine transmitters via reverse transport. Prior studies by us showed that increasing the N-alkyl chain length of N-substituted 4-MA analogues converts 4-MA from a transportable substrate (i.e., releaser) at DAT and NET to a nontransported blocker at these sites. Here, we studied the effects of the individual optical isomers of N-methyl-, N-ethyl-, and N- n-propyl 4-MA on monoamine transporters and abuse-related behavior in rats because action/function might be related to stereochemistry. Uptake inhibition and release assays were conducted in rat brain synaptosomes whereas electrophysiological assessments of drug-transporter interactions were examined using cell-based biosensors. Intracranial-self-stimulation in rats was employed to assess abuse potential in vivo. The experimental evidence demonstrates that S(+) N-methyl 4-MA is a potent and efficacious releaser at DAT, NET, and SERT with the highest abuse potential among the test drugs, whereas R(-) N-methyl 4-MA is a less potent releaser with reduced abuse potential. The S(+)ethyl analogue has decreased efficacy as a releaser at DAT but retains full release activity at NET and SERT with a reduction in abuse-related effects; the R(-)ethyl analogue has a similar profile but is less potent. S(+) N-Propyl 4-MA is a nontransported blocker at DAT and NET but an efficacious releaser at SERT, whereas the R enantiomer is almost inactive. In conclusion, the S enantiomers of the N-alkyl 4-MA analogues are most potent. Lengthening the N-alkyl chain converts compounds from potent nonselective releasers showing abuse-related effects to more selective SERT releasers with no apparent abuse potential.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/farmacologia , Metanfetamina/química , Metanfetamina/farmacologia , Simportadores/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cálcio/metabolismo , Fármacos do Sistema Nervoso Central/síntese química , Modelos Animais de Doenças , Células HEK293 , Humanos , Isomerismo , Masculino , Metanfetamina/síntese química , Estrutura Molecular , Ratos Sprague-Dawley , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
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