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1.
Mikrochim Acta ; 187(6): 315, 2020 05 07.
Article in English | MEDLINE | ID: mdl-32383071

ABSTRACT

Nickel-ferrite nanoparticles (NiFe2O4) were synthesized by a hydrothermal method. They were used to modify a carbon paste electrode (CPE) and to prepare an electrochemical sensor for simultaneous determination of rizatriptan benzoate (RZB) and acetaminophen (AC). The structure and morphology of the bare CPE and modified CPE were studied using field emission scanning electron microscopy, while the structural characterization of NiFe2O4 was performed via X-ray diffraction. In the potential range 0.2-1.2 V, AC and RZB were detected at potentials of 0.5 V and 0.88 V (vs. Ag/AgCl saturated KCl 3 M), respectively. Both calibration plots are linear in the 1 to 90 µM concentration range. The limits of detection (at 3σ) of AC and RZB are 0.49 and 0.44 µM, respectively. The performance of the modified CPE was evaluated by quantifying the two drugs in spiked urine and in tablets. Graphical abstract The modified electrode consist of Nickel-ferrite and graphite by differential pulse voltammetry methods are schematically presented for simultaneous detection of acetaminophen (a painkiller drug) and rizatriptan benzoate (an antimigraine drug) in human urine and tablet samples.


Subject(s)
Acetaminophen/urine , Electrochemical Techniques/methods , Ferric Compounds/chemistry , Metal Nanoparticles/chemistry , Nickel/chemistry , Triazoles/urine , Tryptamines/urine , Acetaminophen/chemistry , Carbon/chemistry , Electrochemical Techniques/instrumentation , Electrodes , Humans , Limit of Detection , Oxidation-Reduction , Tablets/analysis , Triazoles/chemistry , Tryptamines/chemistry
2.
Forensic Sci Int ; 290: 103-110, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30015274

ABSTRACT

4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) is a new psychoactive substance (NPS) of the chemical class of tryptamines. It shows structural similarities to the endogenous neurotransmitter serotonin, and is a serotonergic hallucinogen, affecting emotional, motoric, and cognitive functions. The knowledge about its biotransformation is mandatory to confirm the abuse of the substance by urine analysis in forensic cases. Therefore, phase I metabolites were generated by the use of the pooled human liver microsomes (pHLM) in vitro model and analyzed by high-performance liquid chromatography high-resolution tandem mass spectrometry with information-dependent acquisition (HPLC-IDA-HR-MS/MS). Furthermore, three authentic urine samples was analyzed and results were compared: 12 different in vitro and 4 in vivo metabolites were found. The predominant biotransformation steps observed in vitro were mono- or dihydroxylation of 4-HO-MET, besides demethylation, demethylation in combination with monohydroxylation, formation of a carboxylic acid, deethylation, and oxidative deamination. In vivo, monohydroxylation, and glucuronidation were detected. A metabolic pathway based on these results was proposed. For the analysis of urine samples in forensic cases, the N-oxide metabolite and the HO-alkyl metabolite are recommended as target compounds, besides the glucuronides of 4-HO-MET and the parent compound 4-HO-MET itself.


Subject(s)
Designer Drugs/pharmacokinetics , Psychotropic Drugs/pharmacokinetics , Tryptamines/pharmacokinetics , Biotransformation , Chromatography, Liquid , Female , Forensic Toxicology , Humans , Male , Microsomes, Liver/chemistry , Psychotropic Drugs/urine , Tandem Mass Spectrometry , Tryptamines/urine
3.
Drug Test Anal ; 10(1): 184-195, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28342193

ABSTRACT

Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC-MSn ), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC-HR-MS/MS. 5-MeO-2-Me-DALT (24 phase I and 12 phase II metabolites), 5-MeO-2-Me-ALCHT (24 phase I and 14 phase II metabolites), and 5-MeO-2-Me-DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O-demethylation, hydroxylation, N-dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O-demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N-dealkylation. For SUSAs, GC-MS, LC-MSn , and LC-HR-MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC-MS SUSA, both LC-MS SUSAs were able to detect an intake of 5-MeO-2-Me-ALCHT and 5-MeO-2-Me-DIPT via their metabolites following 1 mg/kg BW administrations and 5-MeO-2-Me-DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd.


Subject(s)
5-Methoxytryptamine/analogs & derivatives , Allyl Compounds/metabolism , Cyclic N-Oxides/metabolism , Gas Chromatography-Mass Spectrometry/methods , Psychotropic Drugs/metabolism , Tandem Mass Spectrometry/methods , Tryptamines/metabolism , 5-Methoxytryptamine/chemistry , 5-Methoxytryptamine/metabolism , 5-Methoxytryptamine/urine , Allyl Compounds/chemistry , Allyl Compounds/urine , Chromatography, Liquid/methods , Chromatography, Liquid/standards , Cyclic N-Oxides/chemistry , Cyclic N-Oxides/urine , Gas Chromatography-Mass Spectrometry/standards , Humans , Psychotropic Drugs/chemistry , Psychotropic Drugs/urine , Substance Abuse Detection/methods , Substance Abuse Detection/standards , Tandem Mass Spectrometry/standards , Tryptamines/chemistry , Tryptamines/urine
4.
Drug Test Anal ; 10(3): 562-574, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28677880

ABSTRACT

The synthetic tryptamine 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) has recently been abused as a hallucinogenic drug in Germany and Switzerland. This study presents a case of 5-MeO-MiPT intoxication and the structural elucidation of metabolites in pooled human liver microsomes (pHLM), blood, and urine. Microsomal incubation experiments were performed using pHLM to detect and identify in vitro metabolites. In August 2016, the police encountered a naked man, agitated and with aggressive behavior on the street. Blood and urine samples were taken at the hospital and his premises were searched. The obtained blood and urine samples were analyzed for in vivo metabolites of 5-MeO-MiPT using liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). The confiscated pills and powder samples were qualitatively analyzed using Fourier transform infrared (FTIR), gas chromatography-mass spectrometry (GC-MS), LC-HRMS/MS, and nuclear magnetic resonance (NMR). 5-MeO-MiPT was identified in 2 of the seized powder samples. General unknown screening detected cocaine, cocaethylene, methylphenidate, ritalinic acid, and 5-MeO-MiPT in urine. Seven different in vitro phase I metabolites of 5-MeO-MiPT were identified. In the forensic case samples, 4 phase I metabolites could be identified in blood and 7 in urine. The 5 most abundant metabolites were formed by demethylation and hydroxylation of the parent compound. 5-MeO-MiPT concentrations in the blood and urine sample were found to be 160 ng/mL and 3380 ng/mL, respectively. Based on the results of this study we recommend metabolites 5-methoxy-N-isopropyltryptamine (5-MeO-NiPT), 5-hydroxy-N-methyl-N-isopropyltryptamine (5-OH-MiPT), 5-methoxy-N-methyl-N-isopropyltryptamine-N-oxide (5-MeO-MiPT-N-oxide), and hydroxy-5-methoxy-N-methyl-N-isopropyltryptamine (OH-5-MeO-MiPT) as biomarkers for the development of new methods for the detection of 5-MeO-MiPT consumption, as they have been present in both blood and urine samples.


Subject(s)
Illicit Drugs/metabolism , Microsomes, Liver/metabolism , Psychotropic Drugs/metabolism , Tryptamines/metabolism , Adult , Chromatography, Liquid/methods , Designer Drugs/metabolism , Designer Drugs/pharmacokinetics , Gas Chromatography-Mass Spectrometry/methods , Humans , Illicit Drugs/blood , Illicit Drugs/urine , Male , Psychotropic Drugs/blood , Psychotropic Drugs/urine , Substance Abuse Detection/methods , Tandem Mass Spectrometry/methods , Tryptamines/blood , Tryptamines/urine
5.
Anal Bioanal Chem ; 409(6): 1681-1695, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27933361

ABSTRACT

Derivatives of N,N-diallyltryptamine (DALT) can be classified as new psychoactive substances. Biotransformation and detectability of 5-fluoro-DALT (5-F-DALT), 7-methyl-DALT (7-Me-DALT), and 5,6-methylenedioxy-DALT (5,6-MD-DALT) are described here. Their metabolites detected in rat urine and pooled human liver microsomes were identified by liquid chromatography (LC)-high resolution (HR)-tandem mass spectrometry (MS/MS). In addition, the human cytochrome-P450 (CYP) isoenzymes involved in the main metabolic steps were identified and detectability tested in urine by the authors' urine screening approaches using GC-MS, LC-MSn, or LC-HR-MS/MS. Aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations could be proposed for all compounds as main pathways. Carboxylation after initial hydroxylation of the methyl group could also be detected for 7-Me-DALT and O-demethylenation was observed for 5,6-MD-DALT. All phase I metabolites were extensively glucuronidated or sulfated. Initial phase I reactions were catalyzed by CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5. Rat urine samples were analyzed following two different low-dose administrations. GC-MS was not able to monitor consumption reliably, but all three compounds are predicted to be detectable in cases of overdose. The LC-MSn and LC-HR-MS/MS approaches were suitable for detecting an intake of all three compounds mainly via their metabolites. However, after the lowest dose, a reliable monitoring could only be achieved for 5-F-DALT via LC-MSn and LC-HR-MS/MS and for 7-Me-DALT via LC-HR-MS/MS. The most abundant targets in both LC-MS screenings were one of two hydroxy-aryl metabolites and both corresponding glucuronides for 5-F-DALT, one N-deallyl hydroxy-aryl, the carboxy, and one dihydroxy-aryl metabolite for 7-Me-DALT, and the demethylenyl metabolite, its oxo metabolite, and glucuronide for 5,6-MD-DALT.


Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Illicit Drugs/urine , Psychotropic Drugs/urine , Tandem Mass Spectrometry/methods , Tryptamines/urine , Animals , Biotransformation , Chromatography, Liquid/methods , Designer Drugs/analysis , Designer Drugs/metabolism , Halogenation , Humans , Illicit Drugs/metabolism , Male , Methylation , Microsomes, Liver/metabolism , Psychotropic Drugs/metabolism , Rats , Rats, Wistar , Substance Abuse Detection/methods , Tryptamines/metabolism
6.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1033-1034: 372-381, 2016 Oct 15.
Article in English | MEDLINE | ID: mdl-27631575

ABSTRACT

A liquid phase microextraction based on hollow fibre followed by liquid chromatographic determination was developed for the extraction and quantitation of the hallucinogenic muscimol from urine samples. Method applicability on polar hallucinogens was also tested on two alkaloids, a psychedelic hallucinogen, tryptamine and a polar amino acid, tryptophan which exists in its charged state in the entire pH range. A multivariate design of experiments was used in which a half fractional factorial approach was applied to screen six factors (donor phase pH, acceptor phase HCl concentration, carrier composition, stirring rate, extraction time and salt content) for their extent of vitality in carrier mediated liquid microextractions. Four factors were deemed essential for the effective extraction of each analyte. The vital factors were further optimized for the extraction of single-spiked analyte solutions using a central composite design. When the simultaneous extraction of analytes was performed under universal factor conditions biased towards maximizing the enrichment of muscimol, a good composite desirability value of 0.687 was obtained. The method was finally applied on spiked urine samples with acceptable enrichments of 4.1, 19.7 and 24.1 obtained for muscimol, tryptophan and tryptamine respectively. Matrix-based calibration curves were used to address matrix effects. The r(2) values of the matrix-based linear regression prediction models ranged from 0.9933 to 0.9986. The linearity of the regression line of the matrix-based calibration curves for each analyte was directly linked to the analyte enrichment repeatability which ranged from an RSD value of 8.3-13.1%. Limits of detection for the developed method were 5.12, 3.10 and 0.21ngmL(-1) for muscimol, tryptophan and tryptamine respectively. The developed method has proven to offer a viable alternative for the quantitation of muscimol in human urine samples.


Subject(s)
Liquid Phase Microextraction/methods , Muscimol/urine , Analysis of Variance , Calibration , Humans , Limit of Detection , Male , Models, Theoretical , Multivariate Analysis , Muscimol/chemistry , Reference Standards , Reproducibility of Results , Tryptamines/urine , Tryptophan/urine , Young Adult
7.
Anal Bioanal Chem ; 407(25): 7831-42, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26297461

ABSTRACT

N,N-Diallyltryptamine (DALT) and 5-methoxy-DALT (5-MeO-DALT) are synthetic tryptamine derivatives commonly referred to as so-called new psychoactive substances (NPS). They have psychoactive effects that may be similar to those of other tryptamine derivatives. The objectives of this work were to study the metabolic fate and detectability, in urine, of DALT and 5-MeO-DALT. For metabolism studies, rat urine obtained after high-dose administration was prepared by precipitation and analyzed by liquid chromatography-high-resolution mass spectrometry (LC-HR-MS-MS). On the basis of the metabolites identified, several aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations thereof are proposed as the main metabolic pathways for both compounds. O-Demethylation of 5-MeO-DALT was also observed, in addition to extensive glucuronidation or sulfation of both compounds after phase I transformation. The cytochrome P450 (CYP) isoenzymes predominantly involved in DALT metabolism were CYP2C19, CYP2D6, and CYP3A4; those mainly involved in 5-MeO-DALT metabolism were CYP1A2, CYP2C19, CYP2D6, and CYP3A4. For detectability studies, rat urine was screened by GC-MS, LC-MS(n), and LC-HR-MS-MS after administration of low doses. LC-MS(n) and LC-HR-MS-MS were deemed suitable for monitoring consumption of both compounds. The most abundant targets were a ring hydroxy metabolite of DALT, the N,O-bis-dealkyl metabolite of 5-MeO-DALT, and their glucuronides. GC-MS enabled screening of DALT by use of its main metabolites only.


Subject(s)
Allyl Compounds/metabolism , Allyl Compounds/urine , Illicit Drugs/metabolism , Illicit Drugs/urine , Psychotropic Drugs/metabolism , Psychotropic Drugs/urine , Tryptamines/metabolism , Tryptamines/urine , Allyl Compounds/chemistry , Animals , Chromatography, Liquid/methods , Cytochrome P-450 Enzyme System/metabolism , Designer Drugs/chemistry , Designer Drugs/metabolism , Gas Chromatography-Mass Spectrometry/methods , Humans , Illicit Drugs/chemistry , Male , Microsomes, Liver/metabolism , Psychotropic Drugs/chemistry , Rats , Rats, Wistar , Tandem Mass Spectrometry/methods , Tryptamines/chemistry
8.
Anal Bioanal Chem ; 406(1): 225-37, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24173660

ABSTRACT

The first synthetic tryptamines have entered the designer drug market in the late 1990s and were distributed as psychedelic recreational drugs. In the meantime, several analogs have been brought onto the market indicating a growing interest in this drug class. So far, only scarce analytical data were available on the detectability of tryptamines in human biosamples. Therefore, the aim of the presented study was the development and full validation of a method for their detection in human urine and plasma and their quantification in human plasma. The liquid chromatography-linear ion trap mass spectrometry method presented covered 37 tryptamines as well as five ß-carbolines, ibogaine, and yohimbine. Compounds were analyzed after protein precipitation of urine or fast liquid-liquid extraction of plasma using an LXQ linear ion trap coupled to an Accela ultra ultra high-performance liquid chromatography system. Data mining was performed via information-dependent acquisition or targeted product ion scan mode with positive electrospray ionization. The assay was selective for all tested substances with limits of detection in urine between 10 and 100 ng/mL and in plasma between 1 and 100 ng/mL. A validated quantification in plasma according to international recommendation could be demonstrated for 33 out of 44 analytes.


Subject(s)
Carbolines , Designer Drugs , Ibogaine , Substance Abuse Detection , Tryptamines , Yohimbine , Carbolines/blood , Carbolines/urine , Chromatography, Liquid/methods , Humans , Ibogaine/blood , Ibogaine/urine , Limit of Detection , Liquid-Liquid Extraction , Spectrometry, Mass, Electrospray Ionization/methods , Tryptamines/blood , Tryptamines/urine , Yohimbine/blood , Yohimbine/urine
9.
Environ Health Prev Med ; 17(2): 87-97, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21655926

ABSTRACT

OBJECTIVE: The effect of a severely stressful situation (sleep restriction and psychological load) on the diurnal changes in novel tryptamine-related compounds (hydroxydiacetyltryptamine, sulphatoxymelatonin, and dihydromelatonin) was evaluated in human subjects for 16 days. METHODS: The subjects were allowed to sleep for 5 h on days three through 12 and for 8 h on the other days. On days three through 12, the subjects were asked to perform a psychological task. The first two and the last 4 days were viewed as control days. A performance test was administered to evaluate the extent of the subjects' fatigue. Total urine was sampled by collecting it into bottles three times a day [(1) during the sleeping period, (2) in the morning, and (3) in the afternoon]. Seven tryptamine-related compounds in urine were assayed using HPLC-fluorometry. RESULTS: The urine melatonin level was high at night and low during the day. In contrast, urinary levels of hydroxydiacetyltryptamine and sulphatoxydiacetyltryptamine were low at night and high during the day. Dihydromelatonin was undetectable in urine during the sleeping period. Sleep restriction and psychological load did not affect diurnal changes in urinary melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels. The concentrations of hydroxymelatonin and sulphatoxymelatonin in urine did not show diurnal changes and decreased gradually during the experimental days. A principal component analysis confirmed the diurnal changes and suggested two novel metabolic pathways: (1) N-acetylserotonin to sulphtoxydiacetyltryptamine via hydroxydiacetyltryptamine, and (2) melatonin to dihydromelatonin. CONCLUSION: Severely stressful situations did not affect diurnal changes in melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels in urine.


Subject(s)
Sleep Deprivation/metabolism , Sleep Deprivation/psychology , Stress, Psychological , Tryptamines/urine , Adult , Analysis of Variance , Chromatography, High Pressure Liquid , Circadian Rhythm , Fatigue/metabolism , Fatigue/urine , Fluorometry , Humans , Male , Melatonin/analogs & derivatives , Melatonin/urine , Principal Component Analysis , Sleep Deprivation/urine , Surveys and Questionnaires , Tryptamines/metabolism , Young Adult
10.
J Nucl Med ; 52(6): 970-7, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21622895

ABSTRACT

UNLABELLED: N,N-dimethyltryptamine (DMT), a strong psychodysleptic drug, has been found in higher plants, shamanic hallucinogenic beverages, and the urine of schizophrenic patients. The aim of this work was to gain better knowledge on the relationship between this drug and hallucinogenic processes by studying DMT behavior in comparison with tryptamine. METHODS: (131)I-labeled DMT and tryptamine were injected into rabbits. γ-Camera and biodistribution studies were performed. Brain uptake, plasma clearance, and renal excretion were assessed for each indolealkylamine. RESULTS: DMT and tryptamine showed different behavior when brain uptake, residence time, and excretion were compared. Labeled DMT entered the brain 10 s after injection, crossed the blood-brain barrier, and bound to receptors; then it was partially renally excreted. It was detected in urine within 24 h after injection and remained in the brain, even after urine excretion ceased; up to 0.1% of the injected dose was detected at 7 d after injection in the olfactory bulb. In contrast, tryptamine was rapidly taken up in the brain and fully excreted 10 min after injection. CONCLUSION: To our knowledge, this is the first demonstration that exogenous DMT remains in the brain for at least 7 d after injection. Although labeled DMT and tryptamine behave as agonists for at least 5-hydroxytryptamine 2A receptor, 5-hydroxytryptamine 2C receptor, trace amine-associated receptor, and σ-1 putative receptor targets, binding to the latter can explain the different behavior of labeled DMT and tryptamine in the brain. The persistence in the brain can be further explained on the basis that DMT and other N,N-dialkyltryptamines are transporter substrates for both the plasma membrane serotonin transporter and the vesicle monoamine transporter 2. Furthermore, storage in vesicles prevents DMT degradation by monoamine oxidase. At high concentrations, DMT is taken up by the serotonin transporter and further stored in vesicles by the vesicle monoamine transporter 2, to be released under appropriate stimuli. Moreover, the (131)I-labeling proved to be a useful tool to perform long-term in vivo studies.


Subject(s)
N,N-Dimethyltryptamine/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Tryptamines/pharmacokinetics , Animals , Brain/diagnostic imaging , Brain/metabolism , Isotope Labeling , Kidney/metabolism , Lipids/chemistry , Magnetic Resonance Spectroscopy , N,N-Dimethyltryptamine/chemical synthesis , N,N-Dimethyltryptamine/urine , Olfactory Bulb/diagnostic imaging , Positron-Emission Tomography , Rabbits , Radionuclide Imaging , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/urine , Receptors, Serotonin/drug effects , Solubility , Tissue Distribution , Tryptamines/chemical synthesis , Tryptamines/urine
11.
J Sep Sci ; 32(23-24): 4143-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19882628

ABSTRACT

A transient ITP-CZE system is proposed for the determination of biogenic amines in urine. The complete separation and identification of dopamine, tyramine (TA), tryptamine (T), serotonin, epinephrine, norepinephrine, and normetanephrine have been achieved in a twofold diluted urine sample (in which the analytes were below the LODs by normal CZE). The tITP preconcentration conditions were created by introducing a 30 mM solution of NaOH, containing 0.1% hydroxypropylcellulose (pH 6.5 adjusted with MES), and 0.1 M HCl before and after the sample zone to work as leading and terminating electrolytes, respectively. This allowed the LODs of direct UV absorption detection to be decreased down to the 10(-8) M level that is comparable with the sensitivity thresholds of LIF detection or inline SPE-CE. The RSDs of migration time and peak area for real-biofluid analysis were in the range of 0.1-4.5% and 0.8-16% (n=3), respectively. Quantification of dopamine, TA, T, and serotonin was performed using internal calibration. To the best of our knowledge, this is the first report on probing urinal biogenic amines and their metabolites by tITP-CZE.


Subject(s)
Biogenic Amines/urine , Electrophoresis, Capillary/methods , Electrophoresis/methods , Adult , Dopamine/urine , Electrophoresis, Capillary/statistics & numerical data , Epinephrine/urine , Humans , Norepinephrine/urine , Normetanephrine/urine , Sensitivity and Specificity , Serotonin/urine , Spectrophotometry, Ultraviolet , Tryptamines/urine , Tyramine/urine
12.
J Chromatogr A ; 1216(36): 6451-8, 2009 Sep 04.
Article in English | MEDLINE | ID: mdl-19646710

ABSTRACT

For the first time, citrate-capped gold nanoparticles (citrate-AuNPs) have been used for the selective extraction of indoleamines--5-hydroxytryptophan (5-HTP), tryptophan (Trp), tryptamine (TA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA)--prior to their analysis by capillary electrophoresis/laser-induced native fluorescence (CE/LINF). The extinction spectra obtained for the citrate-AuNPs in the presence of indoleamines revealed that 5-HTP, 5-HT, and 5-HIAA were extracted mainly because of van der Waals interactions between the indole ring and the citrate-AuNPs (hydrophobic surface), while 5-HT and TA were extracted by electrostatic attractions between the amine group of the indoleamines and the citrate ligands adsorbed on the AuNP surface. The extracted indoleamines could be liberated from the AuNP surface by the addition of high concentrations of 2-mercaptoethanol (2-ME), which binds strongly to the AuNPs. The sensitivity of this method to indoleamines could be significantly enhanced by increasing the AuNP concentration, incubation time, and sample volume. Under optimal extraction and separation conditions, the combination of NP-based extraction and CE-LINF provided 48-, 4077-, 985-, 920-, and 4030-fold improvements in the limits of detection (signal-to-noise ratio of 3) for 5-HTP, Trp, TA, 5-HT, and 5-HIAA as compared to the analysis of five indoleamines by CE-LINF. In addition, this proposed method was successfully used for the determination of TA and 5-HT in urine.


Subject(s)
Electrophoresis, Capillary/methods , Hydroxyindoleacetic Acid/analysis , Lasers , Metal Nanoparticles/chemistry , Spectrometry, Fluorescence/methods , Tryptamines/analysis , Tryptophan/analysis , 5-Hydroxytryptophan/analysis , Adsorption , Citric Acid , Dextran Sulfate , Humans , Light , Linear Models , Male , Mercaptoethanol , Metal Nanoparticles/ultrastructure , Serotonin/blood , Serotonin/urine , Surface Plasmon Resonance , Surface Properties , Tryptamines/blood , Tryptamines/urine , Young Adult
13.
Anal Sci ; 25(6): 759-63, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19531883

ABSTRACT

The optimal conditions for the separation and detection of a mixture of 18 phenethylamine/tryptamine derivatives were determined, using liquid chromatography/UV-absorption (LC/UV) and liquid chromatography/electrospray ionization mass spectrometry (LC/ESI MS) methods, respectively. Complete separation could be achieved within approximately 25 min using gradient elution (A, 0.1% formic acid aqueous solution/pH 2.5; B, acetonitrile). The limit of detection (LOD at S/N = 3) obtained by LC/UV-absorption (absorption wavelength, 280 nm) was in the range from 0.3 to 3 microg/mL. In contrast, when the LC/ESI MS method was used, the LODs for primary, secondary and tertiary amines were in the ranges 0.1-3.0, 0.1-0.2, and 0.05-1.8 microg/mL, respectively. The lower LOD obtained for a tertiary amine can be attributed to the fact that its ionization efficiency (during the ESI process) is better than the others. In order to improve the LOD of a primary/secondary amine, a derivatization procedure was used in which the chemical structure was altered to a secondary/tertiary amine, via a reaction with acetic anhydride. As a result, the LODs for primary/secondary amines could be significantly improved. The characteristic mass fragmentations of the 18 phenethylamine/tryptamine derivatives, as well as the products of the reaction with acetic anhydride, were investigated, and the data were reported. A urine sample was obtained by spiking urine from a volunteer with the 18 derivatives, and after liquid-liquid extraction the sample was examined by LC/UV and LC/ESI MS, respectively. The extraction procedures used for the urine sample and the experimental conditions for the separation and detection were optimized.


Subject(s)
Chromatography, Liquid/methods , Phenethylamines/urine , Spectrometry, Mass, Electrospray Ionization/methods , Spectrophotometry, Ultraviolet/methods , Tryptamines/urine , Chromatography, Liquid/instrumentation , Humans , Phenethylamines/metabolism , Reference Values , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization/instrumentation , Spectrophotometry, Ultraviolet/instrumentation , Tryptamines/metabolism
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 877(8-9): 814-22, 2009 Mar 15.
Article in English | MEDLINE | ID: mdl-19249258

ABSTRACT

During our studies to establish a method for identifying tryptamine-related substances in human urine, we detected three large peaks of unknown origin in an HPLC chromatogram. Fluorometric HPLC and HPLC-TOF-MS/MS analyses led to the identification of these substances as 6-sulphatoxymelatonin, 5-sulphatoxydiacetyltryptamine, and reduced melatonin. This is the first report of the latter two compounds in human urine. Here, we report the results of two fluorometric HPLC assays of these three substances, as well as melatonin, 6-hydroxymelatonin, and 5-hydroxydiacetyltryptamine, using synthesized standards and discuss the possibility that 5-hydroxydiacetyltryptamine (the parent substance of 5-sulphatoxydiacetyltryptamine) and reduced melatonin have radical scavenging activity.


Subject(s)
Chromatography, High Pressure Liquid/methods , Melatonin/analogs & derivatives , Melatonin/chemistry , Tryptamines/chemistry , Adult , Chromatography, High Pressure Liquid/instrumentation , Fluorometry , Humans , Male , Melatonin/chemical synthesis , Melatonin/urine , Tryptamines/chemical synthesis , Tryptamines/urine , Young Adult
15.
Xenobiotica ; 38(12): 1476-86, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18982537

ABSTRACT

1. The in vivo metabolism of alpha-methyltryptamine (AMT), a psychoactive tryptamine analogue, was studied in rats. 2. Male Wistar rats were administered 10 mg kg(-1) AMT orally and 24-h urine fractions were collected. After enzymatic hydrolysis of the urine sample, the metabolites were extracted by liquid-liquid extraction and analysed by gas chromatography/mass spectrometry (GC/MS). 3. 2-Oxo-AMT, 6-hydroxy-AMT, 7-hydroxy-AMT and 1'-hydroxy-AMT were detected as metabolites of AMT.


Subject(s)
Tryptamines/urine , Animals , Gas Chromatography-Mass Spectrometry , Male , Rats , Rats, Wistar , Tryptamines/administration & dosage , Tryptamines/metabolism
16.
Psychiatry Clin Neurosci ; 61(2): 196-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17362440

ABSTRACT

A 23-year-old Japanese woman was brought to the emergency department about 6.5 h after taking liquid and later a half tablet purchased on the street. About 4.5 h prior to presentation, she displayed excited and disorganized behavior. On examination, she was not alert or oriented, with a Glasgow Coma Scale score of 13, did not answer any questions from doctors while smirking and looking around restlessly, and sometimes exhibited echolalia, imitating the speech of doctors. She was given intravenous infusion of fluid for 8 h, then discharged. Gas chromatography-mass spectrometry of urine revealed 5-methoxy-diisopropyltryptamine, 5-methoxy-N-methyltryptamine and an unidentified tryptamine. Identifying chemical products based solely on information of users is insufficient, and urinalysis is necessary in cases potentially involving designer drugs.


Subject(s)
Confusion/chemically induced , Confusion/psychology , Designer Drugs/adverse effects , Substance-Related Disorders/psychology , Tryptamines/adverse effects , 5-Methoxytryptamine/adverse effects , 5-Methoxytryptamine/analogs & derivatives , 5-Methoxytryptamine/urine , Adult , Female , Gas Chromatography-Mass Spectrometry , Glasgow Coma Scale , Humans , Serotonin/adverse effects , Serotonin/analogs & derivatives , Serotonin/urine , Tryptamines/urine
17.
J Chromatogr A ; 1145(1-2): 229-33, 2007 Mar 23.
Article in English | MEDLINE | ID: mdl-17292904

ABSTRACT

A rapid, sensitive and selective method for the determination of tryptophan (Trp), serotonin (5-HT) and psychoactive tryptamines (PATs) by thin-layer chromatography (TLC) with fluorescence detection is proposed. These compounds form fluorophores on the developing plate by heating after spraying with sodium hypochlorite, hydrogen peroxide or potassium hexacyanoferrate(III)-sodium hydroxide reagent. Fluorescent spots (vivid blue) were observed by irradiation with ultraviolet light (365 nm). The detection limits of Trp, 5-HT and PATs were in the range from 0.01 microg to 0.06 microg. This method was effectively applied to the detection of confiscated PAT powder and PAT in abusers' urine samples.


Subject(s)
Chromatography, Thin Layer/methods , Serotonin/analysis , Spectrometry, Fluorescence/methods , Tryptamines/analysis , Tryptophan/analysis , Humans , Molecular Structure , Reproducibility of Results , Serotonin/urine , Substance-Related Disorders/urine , Tryptamines/urine , Tryptophan/urine
18.
Xenobiotica ; 36(9): 807-23, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16971345

ABSTRACT

Almotriptan is a new highly potent selective 5-HT1B/1D receptor agonist developed for the treatment of migraine, and the disposition of almotriptan in different animal species is now addressed in the current study. Almotriptan was well absorbed in rats (69.1%) and dogs (100%) following oral treatment. The absolute bioavailability was variable reflecting different degrees of absorption and first-pass metabolism (18.7-79.6%). The elimination half-life was short and ranged between 0.7 and 3 h. The main route of elimination of almotriptan was urine with 75.6% and 80.4% of the dose recovered over a 168-h period in rats and dogs, respectively. The gamma-aminobutyric acid metabolite formed by oxidation of the pyrrolidine ring was the main metabolite found in urine, faeces, bile, and plasma of rats and in monkey urine. By contrast, the unchanged drug, the indole acetic acid metabolite formed by oxidative deamination of the dimethylaminoethyl group, and the N-oxide metabolite were the main metabolites in dog.


Subject(s)
Haplorhini/metabolism , Serotonin Receptor Agonists/pharmacokinetics , Tryptamines/pharmacokinetics , Animals , Carbon Radioisotopes , Chromatography, High Pressure Liquid , Dogs , Drug Administration Routes , Female , Male , Rats , Rats, Sprague-Dawley , Serotonin Receptor Agonists/blood , Serotonin Receptor Agonists/chemistry , Serotonin Receptor Agonists/urine , Tryptamines/blood , Tryptamines/chemistry , Tryptamines/urine
19.
Article in English | MEDLINE | ID: mdl-16055053

ABSTRACT

We devised a sensitive and simple method to determine alpha-methyltryptamine (AMT) and 5-methoxy-N,N-diisopropyltryptamine (5MeO-DIPT) in whole blood and urine, using gas chromatography-mass spectrometry (GC-MS). AMT and 5MeO-DIPT were extracted using an Extrelut column with an internal standard, bupivacaine, followed by derivatization with acetic anhydride. The derivatized extract was used for GC-MS analysis of EI-SIM mode. The calibration curves of AMT and 5MeO-DIPT were linear in the concentration range from 10 to 750 ng/ml in both blood and urine samples. The method detection limit (MDL) of AMT and 5MeO-DIPT were 1 ng/ml each in whole blood and 5 ng/ml each in urine. This method should be most useful to accurately determine the presence of these drugs in blood and urine in clinical and forensic cases.


Subject(s)
5-Methoxytryptamine/analogs & derivatives , Gas Chromatography-Mass Spectrometry/methods , Tryptamines/analysis , 5-Methoxytryptamine/analysis , 5-Methoxytryptamine/blood , 5-Methoxytryptamine/urine , Humans , Reproducibility of Results , Tryptamines/blood , Tryptamines/urine
20.
J Anal Toxicol ; 29(5): 394-7, 2005.
Article in English | MEDLINE | ID: mdl-16105268

ABSTRACT

In February 2003, the Miami-Dade County Medical Examiner Department reported the first known death in the country related to alpha-methyltryptamine (AMT). AMT is an indole analogue of amphetamine investigated in the 1960s as an antidepressant, stimulant, and monoamine oxidase inhibitor. Today, AMT is recognized as a powerful psychedelic drug among high school and college-aged men and women. Its popularity is partly due to the multitude of anecdotal websites discussing AMT as well as its legality and availability for purchase via the Internet prior to April 2003. Emergency designation of AMT as a Schedule 1 controlled substance by the Drug Enforcement Administration occurred shortly after the death in Miami-Dade County. The case in Miami involved a young college student who, prior to death, advised his roommate that he was "taking hallucinating drugs" and as a result had "discovered the secret of the universe". Approximately 12 h later, the roommate discovered the deceased lying in bed unresponsive. An empty 1-g vial of AMT was recovered from the scene and sent to the toxicology laboratory. Initial screening of urine by enzyme-multiplied immunoassay technique was positive for amphetamines, and the basic drug blood screen detected a small peak later identified by mass spectrometry as AMT. For quantitation, AMT was isolated using solid-phase extraction, derivatized with pentafluoropropionic anhydride, and analyzed using gas chromatography-mass spectrometry. Quantitative analysis was based upon m/z 276, 303, and 466 for AMT and m/z 306, 333, and 496 for the internal standard, 5-methoxy-alpha-methyltryptamine. A linear calibration curve from 50 to 500 ng/mL was used to calculate the concentration of AMT in the samples and controls. Blood, tissue, and gastric specimens were diluted to bring the observed concentration within the limits of the standard curve. Matrix matched controls were extracted and analyzed with each run. Postmortem iliac vein blood revealed 2.0 mg/L, gastric contents (48 g collected at autopsy) contained 9.6 mg total of AMT, liver contained 24.7 mg/kg, and the brain contained 7.8 mg/kg. An additional Medical Examiner case from another jurisdiction revealed 1.5 mg/L in antemortem serum.


Subject(s)
Brain Chemistry , Hallucinogens/poisoning , Tryptamines/poisoning , Adult , Drug Overdose , Fatal Outcome , Gas Chromatography-Mass Spectrometry , Gastrointestinal Contents/chemistry , Hallucinogens/blood , Hallucinogens/urine , Humans , Iliac Vein , Liver/chemistry , Male , Tissue Distribution , Tryptamines/analysis , Tryptamines/blood , Tryptamines/urine
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