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Heather M Antonides - One of the best experts on this subject based on the ideXlab platform.
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analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology method development drug distribution and interpretation of results
Journal of Analytical Toxicology, 2013Co-Authors: Laureen J Marinetti, Heather M AntonidesAbstract:To date, the Toxicology Section of the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory has identified six synthetic cathinones, commonly found in bath salt products, in 43 cases. Thirty-two cases will be reviewed here, including all of the postmortem cases, all of the human performance cases that had blood specimens submitted, and one urine-only human performance case. The following compounds have been confirmed: 3,4-methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), pyrovalerone, pentylone, alpha-pyrrolidinopentiophenone (alpha-PVP) and Methedrone. The method also screens for mephedrone, butylone and 3-fluoromethcathinone. Case demographics show 42 white males and females ranging in age from 19 to 53 years. The remaining case was that of a 34-year-old Hispanic male. The 43 cases represent 17 driving under the influence, two domestic violence, four suicides, 12 overdoses, six accidents, one drug-facilitated assault and one homicide. Data will be presented on the distribution of some of these cathinones in various matrices. After review, blood concentration does not appear to predict outcome regarding fatalities or impairment. The highest MDPV concentration occurred in a suicide by hanging and the highest methylone concentration was in a driver. The confirmation method is a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in multiple reaction monitoring mode. Language: en
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analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology method development drug distribution and interpretation of results
Journal of Analytical Toxicology, 2013Co-Authors: Laureen J Marinetti, Heather M AntonidesAbstract:To date, the Toxicology Section of the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory has identified six synthetic cathinones, commonly found in bath salt products, in 43 cases. Thirty-two cases will be reviewed here, including all of the postmortem cases, all of the human performance cases that had blood specimens submitted, and one urine-only human performance case. The following compounds have been confirmed: 3,4-methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), pyrovalerone, pentylone, alpha-pyrrolidinopentiophenone (alpha-PVP) and Methedrone. The method also screens for mephedrone, butylone and 3-fluoromethcathinone. Case demographics show 42 white males and females ranging in age from 19 to 53 years. The remaining case was that of a 34-year-old Hispanic male. The 43 cases represent 17 driving under the influence, two domestic violence, four suicides, 12 overdoses, six accidents, one drug-facilitated assault and one homicide. Data will be presented on the distribution of some of these cathinones in various matrices. After review, blood concentration does not appear to predict outcome regarding fatalities or impairment. The highest MDPV concentration occurred in a suicide by hanging and the highest methylone concentration was in a driver. The confirmation method is a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in multiple reaction monitoring mode.
Magí Farré - One of the best experts on this subject based on the ideXlab platform.
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Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in Humans.
Pharmaceuticals (Basel Switzerland), 2021Co-Authors: Esther Papaseit, Eulàlia Olesti, Rafael De La Torre, Clara Pérez-mañá, Francina Fonseca, Marta Torrens, Marc Grifell, Mireia Ventura, Magí FarréAbstract:Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100-200 mg; mean 150 mg) or intranasally (n = 5, 50-100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.
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dose response pharmacological study of mephedrone and its metabolites pharmacokinetics serotoninergic effects and impact of cyp2d6 genetic variation
Clinical Pharmacology & Therapeutics, 2019Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Mitona Pujadas, Marta Torrens, Marcel Li Carbo, Clara Perezmana, Samanta Yuberolahoz, Óscar J. PozoAbstract:Mephedrone (MEPH), the most widely consumed synthetic cathinone, has been associated with acute toxicity episodes. The aim of this report was to study its metabolic disposition and the impact of genetic variation of CYP2D6 on MEPH metabolism, in a dose range compatible with its recreational use. A randomized, crossover, phase I clinical trial was performed. Subjects received 50 and 100 mg (n = 3) and 150 and 200 mg (n = 6) of mephedrone and were genetically and phenotypically characterized for the CYP2D6 allelic variation. Our results showed a linear kinetics of mephedrone at the dose range assayed: plasma concentrations, cardiovascular and subjective effects, and blood serotonin concentrations all correlated in a dose-dependent manner. Mephedrone metabolic disposition is mediated by CYP2D6. Mephedrone pharmacology presented a linear dose-dependence within the range of doses tested. The metabolism of mephedrone by CYP2D6 implies that recreational users with no or low CYP2D6 functionality are exposed to unwanted acute toxicity episodes.
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Mephedrone Concentrations in Cases of Clinical Intoxication.
Current pharmaceutical design, 2018Co-Authors: Esther Papaseit, Eulàlia Olesti, Rafael De La Torre, Marta Torrens, Magí FarréAbstract:Background Mephedrone (4-methylmethcathinone, 4-MMC), a ring-substituted synthetic cathinone derivative has become established as a permanent illicit drug in the dynamic new psychoactive substances (NPS) scene. Objective This review summarizes current knowledge on mephedrone concentrations in biological samples from cases of acute intoxications (fatal and non-fatal), pharmacokinetics studies, wastewater and anonymous pooled urine analysis in order to provide an overview of the reliable scientific knowledge on toxicokinetics of mephedrone in humans. Method The PubMed® database complemented with Google Scholar® was systematically searched to find published cases of mephedrone intoxications. The searches were done using the keyword "mephedrone OR 4- methylmethcathinone" in association to each of the following strategies: i) "intoxication OR poisoning"; ii) "(blood OR serum OR plasma") OR "urine" OR ("saliva OR oral fluid") OR "hair"; iii) "forensic toxicology samples"; iv) "wastewater OR sewage OR pooled urine" and v) "toxicity OR death OR fatal". Results Since 2010, a total of 97 fatal cases and 57 non-fatal intoxication cases were identified that presented mephedrone concentrations in human biological matrices attributed directly or indirectly to mephedrone. Typical subjects involved were young male with concomitant use of other drugs (psychostimulants, cannabis, alcohol and other depressants). Mephedrone mean blood concentration from fatal cases was 2,663 ng/mL (range 51-22,000 ng/mL), from non-fatal cases was 166 ng/mL (range, 13-412 ng/mL), that resulted in a similar range from data found in controlled studies with no acute toxicity associated (135 ng/mL, range 52-218 ng/mL). Forensic epidemiology studies based on wastewater and anonymous pooled urine analysis point towards similar variations in use (nightclub scene) to those self-reported in surveys and questioners. Conclusion Mephedrone blood concentrations in cases of fatal intoxications were higher than in non-fatal cases. In both cases, great variability in mephedrone concentration potentially attributable to interindividual differences in pharmacokinetics-pharmacodynamics and poly-drug use complicates the interpretation of the forensic toxicological analysis.
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Pharmacokinetics of Mephedrone and Its Metabolites in Human by LC-MS/MS
The AAPS Journal, 2017Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Aristotelis Krotonoulas, Mitona Pujadas, Rafael De La Torre, Óscar J. PozoAbstract:Mephedrone is a synthetic cathinone consumed as a recreational drug. Recently, it was identified several of its metabolites in vivo in humans but there is little information about its pharmacokinetics in plasma and urine. Although several analytical methods have been proposed for mephedrone quantification in different matrices, none are available for its metabolites. Therefore, the aim of the study was to develop and validate an analytical method using liquid chromatography-tandem mass spectrometry for the quantification of mephedrone, nor-mephedrone, N -succinyl-nor-mephedrone, 1′-dihydro-mephedrone, and 4′-carboxy-mephedrone. The method was validated in human plasma and urine and in rat brain homogenates. Six healthy male subjects, recreational users of new psychoactive substances, ingested 150 mg of mephedrone within the context of a clinical trial. 4′-Carboxy-mephedrone, followed by nor-mephedrone, was the most abundant metabolites found in plasma. Dihydro-mephedrone represented 10% of the amount of mephedrone in plasma and N -succinyl-nor-mephedrone was the metabolite eliminated with the longer half-life of 8.2 h. In urine, 4′-carboxy-mephedrone was the main metabolite excreted with amounts recovered being about 10 times those of mephedrone. Additionally, the validated method was used to test metabolite ability to cross the blood-brain barrier in vivo in rats with mephedrone and nor-mephedrone as the main active compounds present in the brain. The method described is useful for the determinations of mephedrone and metabolites in biological samples. Graphical Abstract ᅟ
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pharmacokinetics of mephedrone and its metabolites in human by lc ms ms
Aaps Journal, 2017Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Aristotelis Krotonoulas, Mitona Pujadas, Rafael De La Torre, Óscar J. PozoAbstract:Mephedrone is a synthetic cathinone consumed as a recreational drug. Recently, it was identified several of its metabolites in vivo in humans but there is little information about its pharmacokinetics in plasma and urine. Although several analytical methods have been proposed for mephedrone quantification in different matrices, none are available for its metabolites. Therefore, the aim of the study was to develop and validate an analytical method using liquid chromatography-tandem mass spectrometry for the quantification of mephedrone, nor-mephedrone, N-succinyl-nor-mephedrone, 1′-dihydro-mephedrone, and 4′-carboxy-mephedrone. The method was validated in human plasma and urine and in rat brain homogenates. Six healthy male subjects, recreational users of new psychoactive substances, ingested 150 mg of mephedrone within the context of a clinical trial. 4′-Carboxy-mephedrone, followed by nor-mephedrone, was the most abundant metabolites found in plasma. Dihydro-mephedrone represented 10% of the amount of mephedrone in plasma and N-succinyl-nor-mephedrone was the metabolite eliminated with the longer half-life of 8.2 h. In urine, 4′-carboxy-mephedrone was the main metabolite excreted with amounts recovered being about 10 times those of mephedrone. Additionally, the validated method was used to test metabolite ability to cross the blood-brain barrier in vivo in rats with mephedrone and nor-mephedrone as the main active compounds present in the brain. The method described is useful for the determinations of mephedrone and metabolites in biological samples.
Esther Papaseit - One of the best experts on this subject based on the ideXlab platform.
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Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in Humans.
Pharmaceuticals (Basel Switzerland), 2021Co-Authors: Esther Papaseit, Eulàlia Olesti, Rafael De La Torre, Clara Pérez-mañá, Francina Fonseca, Marta Torrens, Marc Grifell, Mireia Ventura, Magí FarréAbstract:Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100-200 mg; mean 150 mg) or intranasally (n = 5, 50-100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.
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Mephedrone and Alcohol Interactions in Humans.
Frontiers in pharmacology, 2020Co-Authors: Esther Papaseit, Eulàlia Olesti, Clara Pérez-mañá, Elizabeth B. De Sousa Fernandes Perna, Julian Mateus, Kim P. C. Kuypers, Eef L. Theunissen, Francina Fonseca, Marta Torrens, Jan RamaekersAbstract:Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of New Psychoactive Substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in humans. Eleven male volunteers participated as outpatients in four experimental sessions in a double-blind, randomized, cross-over, and placebo-controlled clinical trial. Participants received a single oral dose of 200 mg of mephedrone plus 0.8 g/kg of alcohol (combination condition); 200 mg of mephedrone plus placebo alcohol (mephedrone condition); placebo mephedrone plus 0.8 g/kg of ethanol (alcohol condition); and placebo mephedrone plus placebo alcohol (placebo condition). Outcome variables included physiological (blood pressure, heart rate, temperature, and pupil diameter), psychomotor (Maddox wing), subjective (visual analogue scales-VAS, ARCI-49 item short form, and VESSPA questionnaire), and pharmacokinetic parameters (mephedrone and ethanol concentrations). The study was registered in ClinicalTrials.gov, number NCT02294266. The mephedrone and alcohol combination produced an increase in the cardiovascular effects of mephedrone and induced a more intense feeling of euphoria and well-being in comparison to the two drugs alone. Mephedrone reduced the sedative effects produced by alcohol. These results are similar to those obtained when other psychostimulants such as amphetamines and MDMA are combined simultaneously with alcohol. The abuse liability of mephedrone combined with alcohol is greater than that induced by mephedrone alone.
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dose response pharmacological study of mephedrone and its metabolites pharmacokinetics serotoninergic effects and impact of cyp2d6 genetic variation
Clinical Pharmacology & Therapeutics, 2019Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Mitona Pujadas, Marta Torrens, Marcel Li Carbo, Clara Perezmana, Samanta Yuberolahoz, Óscar J. PozoAbstract:Mephedrone (MEPH), the most widely consumed synthetic cathinone, has been associated with acute toxicity episodes. The aim of this report was to study its metabolic disposition and the impact of genetic variation of CYP2D6 on MEPH metabolism, in a dose range compatible with its recreational use. A randomized, crossover, phase I clinical trial was performed. Subjects received 50 and 100 mg (n = 3) and 150 and 200 mg (n = 6) of mephedrone and were genetically and phenotypically characterized for the CYP2D6 allelic variation. Our results showed a linear kinetics of mephedrone at the dose range assayed: plasma concentrations, cardiovascular and subjective effects, and blood serotonin concentrations all correlated in a dose-dependent manner. Mephedrone metabolic disposition is mediated by CYP2D6. Mephedrone pharmacology presented a linear dose-dependence within the range of doses tested. The metabolism of mephedrone by CYP2D6 implies that recreational users with no or low CYP2D6 functionality are exposed to unwanted acute toxicity episodes.
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Mephedrone Concentrations in Cases of Clinical Intoxication.
Current pharmaceutical design, 2018Co-Authors: Esther Papaseit, Eulàlia Olesti, Rafael De La Torre, Marta Torrens, Magí FarréAbstract:Background Mephedrone (4-methylmethcathinone, 4-MMC), a ring-substituted synthetic cathinone derivative has become established as a permanent illicit drug in the dynamic new psychoactive substances (NPS) scene. Objective This review summarizes current knowledge on mephedrone concentrations in biological samples from cases of acute intoxications (fatal and non-fatal), pharmacokinetics studies, wastewater and anonymous pooled urine analysis in order to provide an overview of the reliable scientific knowledge on toxicokinetics of mephedrone in humans. Method The PubMed® database complemented with Google Scholar® was systematically searched to find published cases of mephedrone intoxications. The searches were done using the keyword "mephedrone OR 4- methylmethcathinone" in association to each of the following strategies: i) "intoxication OR poisoning"; ii) "(blood OR serum OR plasma") OR "urine" OR ("saliva OR oral fluid") OR "hair"; iii) "forensic toxicology samples"; iv) "wastewater OR sewage OR pooled urine" and v) "toxicity OR death OR fatal". Results Since 2010, a total of 97 fatal cases and 57 non-fatal intoxication cases were identified that presented mephedrone concentrations in human biological matrices attributed directly or indirectly to mephedrone. Typical subjects involved were young male with concomitant use of other drugs (psychostimulants, cannabis, alcohol and other depressants). Mephedrone mean blood concentration from fatal cases was 2,663 ng/mL (range 51-22,000 ng/mL), from non-fatal cases was 166 ng/mL (range, 13-412 ng/mL), that resulted in a similar range from data found in controlled studies with no acute toxicity associated (135 ng/mL, range 52-218 ng/mL). Forensic epidemiology studies based on wastewater and anonymous pooled urine analysis point towards similar variations in use (nightclub scene) to those self-reported in surveys and questioners. Conclusion Mephedrone blood concentrations in cases of fatal intoxications were higher than in non-fatal cases. In both cases, great variability in mephedrone concentration potentially attributable to interindividual differences in pharmacokinetics-pharmacodynamics and poly-drug use complicates the interpretation of the forensic toxicological analysis.
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Pharmacokinetics of Mephedrone and Its Metabolites in Human by LC-MS/MS
The AAPS Journal, 2017Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Aristotelis Krotonoulas, Mitona Pujadas, Rafael De La Torre, Óscar J. PozoAbstract:Mephedrone is a synthetic cathinone consumed as a recreational drug. Recently, it was identified several of its metabolites in vivo in humans but there is little information about its pharmacokinetics in plasma and urine. Although several analytical methods have been proposed for mephedrone quantification in different matrices, none are available for its metabolites. Therefore, the aim of the study was to develop and validate an analytical method using liquid chromatography-tandem mass spectrometry for the quantification of mephedrone, nor-mephedrone, N -succinyl-nor-mephedrone, 1′-dihydro-mephedrone, and 4′-carboxy-mephedrone. The method was validated in human plasma and urine and in rat brain homogenates. Six healthy male subjects, recreational users of new psychoactive substances, ingested 150 mg of mephedrone within the context of a clinical trial. 4′-Carboxy-mephedrone, followed by nor-mephedrone, was the most abundant metabolites found in plasma. Dihydro-mephedrone represented 10% of the amount of mephedrone in plasma and N -succinyl-nor-mephedrone was the metabolite eliminated with the longer half-life of 8.2 h. In urine, 4′-carboxy-mephedrone was the main metabolite excreted with amounts recovered being about 10 times those of mephedrone. Additionally, the validated method was used to test metabolite ability to cross the blood-brain barrier in vivo in rats with mephedrone and nor-mephedrone as the main active compounds present in the brain. The method described is useful for the determinations of mephedrone and metabolites in biological samples. Graphical Abstract ᅟ
Sarah Kerrigan - One of the best experts on this subject based on the ideXlab platform.
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identification and quantification of synthetic cathinones in blood and urine using liquid chromatography quadrupole time of flight lc q tof mass spectrometry
Journal of Chromatography B, 2016Co-Authors: Lindsay Glicksberg, Kelsie Bryand, Sarah KerriganAbstract:Abstract Synthetic cathinones continue to present a formidable challenge to forensic toxicology laboratories despite the fact that they are often encountered in impaired driving and death investigations. Due to limitations in immunoassay-based screening technologies, many forensic toxicology laboratories must rely on more labor intensive chromatographic-based screening approaches in order to detect these drugs in biological evidence. Solid phase extraction (SPE) and liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry were used to identify twenty-two synthetic cathinones in urine and blood. Target drugs included methcathinone, ethcathinone, pentedrone, buphedrone, 3-fluoromethcathinone (3-FMC), 4-fluoromethcathinone (4-FMC), 4-methylethcathinone (4-MEC), 4-ethylmethcathinone (4-EMC), mephedrone, Methedrone, 3,4-dimethylmethcathinone (3,4-DMMC), ethylone, butylone, pentylone, eutylone, methylone, methylenedioxypyrovalerone (MDPV), 4-methylpyrrolidinobutiophenone (MPBP), 3,4-methylenedioxypyrrolidinobutiophenone (MDPBP), α-pyrrolidinopentiphenone (α-PVP), pyrovalerone, and naphyrone. A total of nine deuterated internal standards were employed. Using traditional reversed phase chromatography all positional isomers, including 3-FMC and 4-FMC, were separated in 12 min. The procedure was validated in accordance with the Scientific Working Group for Forensic Toxicology (SWGTOX) Standard Practices for Method Validation. Extraction efficiencies were 84–104% and 81–93% in urine and blood, respectively. Limits of quantitation in both matrices were 0.25–5 ng/mL. Precision, bias and matrix effect were all within acceptable thresholds and the assay was free from more than fifty interferences. The validated method was used to identify cathinones in authentic urine case samples (n = 20) and these results highlight important considerations for cathinone stability and the subsequent interpretation of results.
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Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2016Co-Authors: Lindsay Glicksberg, Kelsie Bryand, Sarah KerriganAbstract:Abstract Synthetic cathinones continue to present a formidable challenge to forensic toxicology laboratories despite the fact that they are often encountered in impaired driving and death investigations. Due to limitations in immunoassay-based screening technologies, many forensic toxicology laboratories must rely on more labor intensive chromatographic-based screening approaches in order to detect these drugs in biological evidence. Solid phase extraction (SPE) and liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry were used to identify twenty-two synthetic cathinones in urine and blood. Target drugs included methcathinone, ethcathinone, pentedrone, buphedrone, 3-fluoromethcathinone (3-FMC), 4-fluoromethcathinone (4-FMC), 4-methylethcathinone (4-MEC), 4-ethylmethcathinone (4-EMC), mephedrone, Methedrone, 3,4-dimethylmethcathinone (3,4-DMMC), ethylone, butylone, pentylone, eutylone, methylone, methylenedioxypyrovalerone (MDPV), 4-methylpyrrolidinobutiophenone (MPBP), 3,4-methylenedioxypyrrolidinobutiophenone (MDPBP), α-pyrrolidinopentiphenone (α-PVP), pyrovalerone, and naphyrone. A total of nine deuterated internal standards were employed. Using traditional reversed phase chromatography all positional isomers, including 3-FMC and 4-FMC, were separated in 12 min. The procedure was validated in accordance with the Scientific Working Group for Forensic Toxicology (SWGTOX) Standard Practices for Method Validation. Extraction efficiencies were 84–104% and 81–93% in urine and blood, respectively. Limits of quantitation in both matrices were 0.25–5 ng/mL. Precision, bias and matrix effect were all within acceptable thresholds and the assay was free from more than fifty interferences. The validated method was used to identify cathinones in authentic urine case samples (n = 20) and these results highlight important considerations for cathinone stability and the subsequent interpretation of results.
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thermal degradation of synthetic cathinones implications for forensic toxicology
Journal of Analytical Toxicology, 2015Co-Authors: Sarah Kerrigan, Megan Savage, Cassandra Cavazos, Paige BellaAbstract:The synthetic cathinones represent an important class of designer drugs. The widespread attention and publicity associated with these psychostimulants have resulted in numerous legislative actions at state and federal levels throughout the USA. These amphetamine-like compounds are characterized by a β-keto functional group. Although the synthetic cathinones share many properties of their phenethylamine counterparts, the presence of the ketone moiety is responsible for a number of unique and distinct differences in terms of their chemical characteristics and properties. Thermal degradation of methcathinone was first reported several decades ago but has received limited attention. In this study, we identified in situ thermal degradation products for 18 cathinones during gas chromatography-mass spectrometry (GC-MS) analysis. Oxidative degradation arises from the loss of two hydrogens, yielding a characteristic 2 Da mass shift. Degradation products were characterized by prominent iminium base peaks with mass-to-charge ratios 2 Da lower than the parent drug, and in the case of the pyrrolidine-containing cathinones, prominent molecular ions arising from the 2,3-enamine. Chromatographic and mass spectroscopic data are described for 4-ethylmethcathinone, 4-methylethcathinone, buphedrone, butylone, ethcathinone, ethylone, flephedrone, 3,4-methylenedioxy-α-pyrrolidinobutiophenone, 3,4-methylenedioxypyrovalerone, mephedrone, methcathinone, Methedrone, methylone, 4-methyl-α-pyrrolidinobutiophenone, naphyrone, pentedrone, pentylone and pyrovalerone. Degradation was minimized by lowering injection temperatures, residence time in the inlet and eliminating active sites during chromatographic analysis. Chromatographic and mass spectral data for the cathinone degradation products are presented and discussed within the context of forensic toxicological analysis, selection of appropriate instrumental methods and implications for the interpretation of results.
Rafael De La Torre - One of the best experts on this subject based on the ideXlab platform.
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Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in Humans.
Pharmaceuticals (Basel Switzerland), 2021Co-Authors: Esther Papaseit, Eulàlia Olesti, Rafael De La Torre, Clara Pérez-mañá, Francina Fonseca, Marta Torrens, Marc Grifell, Mireia Ventura, Magí FarréAbstract:Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100-200 mg; mean 150 mg) or intranasally (n = 5, 50-100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.
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Mephedrone Concentrations in Cases of Clinical Intoxication.
Current pharmaceutical design, 2018Co-Authors: Esther Papaseit, Eulàlia Olesti, Rafael De La Torre, Marta Torrens, Magí FarréAbstract:Background Mephedrone (4-methylmethcathinone, 4-MMC), a ring-substituted synthetic cathinone derivative has become established as a permanent illicit drug in the dynamic new psychoactive substances (NPS) scene. Objective This review summarizes current knowledge on mephedrone concentrations in biological samples from cases of acute intoxications (fatal and non-fatal), pharmacokinetics studies, wastewater and anonymous pooled urine analysis in order to provide an overview of the reliable scientific knowledge on toxicokinetics of mephedrone in humans. Method The PubMed® database complemented with Google Scholar® was systematically searched to find published cases of mephedrone intoxications. The searches were done using the keyword "mephedrone OR 4- methylmethcathinone" in association to each of the following strategies: i) "intoxication OR poisoning"; ii) "(blood OR serum OR plasma") OR "urine" OR ("saliva OR oral fluid") OR "hair"; iii) "forensic toxicology samples"; iv) "wastewater OR sewage OR pooled urine" and v) "toxicity OR death OR fatal". Results Since 2010, a total of 97 fatal cases and 57 non-fatal intoxication cases were identified that presented mephedrone concentrations in human biological matrices attributed directly or indirectly to mephedrone. Typical subjects involved were young male with concomitant use of other drugs (psychostimulants, cannabis, alcohol and other depressants). Mephedrone mean blood concentration from fatal cases was 2,663 ng/mL (range 51-22,000 ng/mL), from non-fatal cases was 166 ng/mL (range, 13-412 ng/mL), that resulted in a similar range from data found in controlled studies with no acute toxicity associated (135 ng/mL, range 52-218 ng/mL). Forensic epidemiology studies based on wastewater and anonymous pooled urine analysis point towards similar variations in use (nightclub scene) to those self-reported in surveys and questioners. Conclusion Mephedrone blood concentrations in cases of fatal intoxications were higher than in non-fatal cases. In both cases, great variability in mephedrone concentration potentially attributable to interindividual differences in pharmacokinetics-pharmacodynamics and poly-drug use complicates the interpretation of the forensic toxicological analysis.
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Pharmacokinetics of Mephedrone and Its Metabolites in Human by LC-MS/MS
The AAPS Journal, 2017Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Aristotelis Krotonoulas, Mitona Pujadas, Rafael De La Torre, Óscar J. PozoAbstract:Mephedrone is a synthetic cathinone consumed as a recreational drug. Recently, it was identified several of its metabolites in vivo in humans but there is little information about its pharmacokinetics in plasma and urine. Although several analytical methods have been proposed for mephedrone quantification in different matrices, none are available for its metabolites. Therefore, the aim of the study was to develop and validate an analytical method using liquid chromatography-tandem mass spectrometry for the quantification of mephedrone, nor-mephedrone, N -succinyl-nor-mephedrone, 1′-dihydro-mephedrone, and 4′-carboxy-mephedrone. The method was validated in human plasma and urine and in rat brain homogenates. Six healthy male subjects, recreational users of new psychoactive substances, ingested 150 mg of mephedrone within the context of a clinical trial. 4′-Carboxy-mephedrone, followed by nor-mephedrone, was the most abundant metabolites found in plasma. Dihydro-mephedrone represented 10% of the amount of mephedrone in plasma and N -succinyl-nor-mephedrone was the metabolite eliminated with the longer half-life of 8.2 h. In urine, 4′-carboxy-mephedrone was the main metabolite excreted with amounts recovered being about 10 times those of mephedrone. Additionally, the validated method was used to test metabolite ability to cross the blood-brain barrier in vivo in rats with mephedrone and nor-mephedrone as the main active compounds present in the brain. The method described is useful for the determinations of mephedrone and metabolites in biological samples. Graphical Abstract ᅟ
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pharmacokinetics of mephedrone and its metabolites in human by lc ms ms
Aaps Journal, 2017Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Aristotelis Krotonoulas, Mitona Pujadas, Rafael De La Torre, Óscar J. PozoAbstract:Mephedrone is a synthetic cathinone consumed as a recreational drug. Recently, it was identified several of its metabolites in vivo in humans but there is little information about its pharmacokinetics in plasma and urine. Although several analytical methods have been proposed for mephedrone quantification in different matrices, none are available for its metabolites. Therefore, the aim of the study was to develop and validate an analytical method using liquid chromatography-tandem mass spectrometry for the quantification of mephedrone, nor-mephedrone, N-succinyl-nor-mephedrone, 1′-dihydro-mephedrone, and 4′-carboxy-mephedrone. The method was validated in human plasma and urine and in rat brain homogenates. Six healthy male subjects, recreational users of new psychoactive substances, ingested 150 mg of mephedrone within the context of a clinical trial. 4′-Carboxy-mephedrone, followed by nor-mephedrone, was the most abundant metabolites found in plasma. Dihydro-mephedrone represented 10% of the amount of mephedrone in plasma and N-succinyl-nor-mephedrone was the metabolite eliminated with the longer half-life of 8.2 h. In urine, 4′-carboxy-mephedrone was the main metabolite excreted with amounts recovered being about 10 times those of mephedrone. Additionally, the validated method was used to test metabolite ability to cross the blood-brain barrier in vivo in rats with mephedrone and nor-mephedrone as the main active compounds present in the brain. The method described is useful for the determinations of mephedrone and metabolites in biological samples.
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GC-MS Quantification Method for Mephedrone in Plasma and Urine: Application to Human Pharmacokinetics.
Journal of analytical toxicology, 2017Co-Authors: Eulàlia Olesti, Magí Farré, Esther Papaseit, Mitona Pujadas, Óscar J. Pozo, Clara Pérez-mañá, Rafael De La TorreAbstract:Increasing consumption has been observed among young people of new psychoactive substances, including synthetic cathinone derivatives. The most well known of these is mephedrone whose use has been related to acute intoxication and fatality. Several methods able to detect mephedrone have been reported, although to date, none have been applied to human pharmacokinetic studies in a controlled setting. We developed a gas chromatography-mass spectrometry technique for mephedrone quantification in human plasma and urine. Plasma after deproteinization and urine were submitted to a liquid-liquid extraction and derivatization of the extract with MSTFA prior to analysis. Calibration curves covered concentration ranges in plasma between 5 and 300 ng/mL and in urine between 20 and 1,500 ng/mL. The method has been successfully applied to biological samples obtained from a pilot clinical trial intended to evaluate the human pharmacology of mephedrone and its relative bioavailability and pharmacokinetics. Six healthy males were administered 150 mg of mephedrone by the oral route in a randomized, double-blind, cross-over controlled trial. Peak plasma concentration (Cmax = 122.6 ± 32.9 ng/mL) was reached at 1 hour (0.5-2 h) post-drug administration. Mephedrone showed a rapid elimination half-life (t1/2 = 2.2 h) compared to other psychostimulants. Less than 15% of the dose was excreted in urine as a free-form. Mephedrone concentrations displayed a relevant inter-subject variability.