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1.
Anal Chim Acta ; 1108: 89-97, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32222248

RESUMO

Ingested drugs can be taken up into nails and hairs from the bloodstream and these drugs can be stably retained over several months or more. Free edges of nails can often be used as a specimen to prove drug intake. However, the mechanism of drug uptake into the nails is unclear. Although it is presumed that there are horizontal uptake routes at the nail root and vertical uptake routes at the nail bed against the direction of growth, three-dimensional distribution analysis is required to verify this phenomenon. Herein, we first developed a method to measure the three-dimensional distribution of drugs in the nails using the combination of micro-segmentation of nails (0.2 × 1.5 × 0.06 mm size) and highly sensitive quantification of drugs by LC-MS/MS. Carbinoxamine was administered as a model compound to a subject in a single dose, and then the free edges of big toenails were collected every several weeks over a year. The three-dimensional distribution of carbinoxamine in each free edge was visualized and arranged along the collection period. Carbinoxamine was localized in the lower layer during the early collection period (up to 78 days after drug ingestion) and in the upper and middle layers later (134 days or later). The changes in the drug distribution in the nails along the collection period implied that two-way drug uptake takes place in the whole nail through both the nail bed and the nail root simultaneously. The developed analytical method could be useful to elucidate the mechanism of drug uptake into the nails.

2.
Drug Test Anal ; 12(4): 439-448, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31797567

RESUMO

The metabolism of a new synthetic opioid tetrahydrofuranylfentanyl (THF-fentanyl) was investigated using fresh human hepatocytes. Fourteen metabolites of THF-fentanyl, such as tetrahydrofuran ring-opened metabolites, desphenethylated metabolites, hydroxylated metabolites, and hydroxylated and methoxylated metabolites and their glucuronides, were detected in the culture medium of hepatocytes incubated with THF-fentanyl. Six metabolites, i.e. desphenethylated metabolite, 4'-hydroxy-THF-fentanyl, ß-hydroxy-THF-fentanyl, 4'-hydroxy-3'-methoxy-THF-fentanyl, ring-opened alcohol metabolite, and ring-opened carboxylic acid metabolite, were identified via chemically synthesized authentic standards. A ring-opened alcohol metabolite and a ring-opened carboxylic acid metabolite are thought to be formed by reduction or oxidation of the intermediate aldehyde, which was formed by ring-opening of the metabolite hydroxylated at the carbon atom adjacent to the oxygen atom of the tetrahydrofuran ring. A ring-opened carboxylic acid metabolite was the main metabolite of THF-fentanyl based on the peak intensity.

3.
Analyst ; 144(23): 6928-6935, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31661540

RESUMO

Synthetic cannabinoids (SCs) are a major category of new psychoactive substances that are frequently distributed after addition to plants. To date, various SCs with small differences in their chemical structures have prevailed in the illegal drug market. Thus, the development of a method for rapid detection with high discrimination capability is critically important for the forensic field. Vibrational spectroscopy is a possible analytical technique for this purpose because it can sensitively reflect differences among chemical structures. In this study, we applied surface-enhanced Raman scattering (SERS) with gold nanoparticle co-aggregation in a wet system to plant samples containing SCs. The experimental protocol used was simple and involved only mixing of the sample with several other solutions. It was possible to detect SERS spectra from various stock solutions of SCs by this method. The method was then applied to street samples containing SCs. Some of the plant samples containing SCs did not produce significant SERS signals even though stock solutions of the same SCs did produce SERS spectra. We investigated the reason for this discrepancy and speculated that the solubility in aqueous solutions was a factor determining whether a significant SERS signal could be detected or not. According to this hypothesis, minimal sample pre-treatment methods were applied. This allowed for the detection of SERS spectra from the examined plant samples. The developed approach is a powerful method for screening analysis of SCs in plant fragments.

4.
Yakugaku Zasshi ; 139(5): 699-704, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31061338

RESUMO

Human hepatocytes possess a wider range of phase I and II drug-metabolizing enzyme activities than other liver tissue-derived products, such as human liver microsomes. Thus, hepatocytes may be useful for predicting the in vivo metabolic fate of new drugs of abuse in humans. Recently, new types of human hepatocytes have been made commercially available for use in drug metabolism studies, such as a liver tumor-derived cell line (HepaRG), and a human induced pluripotent stem cell-derived hepatocyte (h-iPS-HEP). In our laboratory, HepaRG has been used to elucidate the metabolic pathways of XLR-11, a synthetic cannabinoid, and its thermal degradant. In addition, the potential of h-iPS-HEP to metabolize drugs was assessed using fentanyl as a model drug, and indeed, h-iPS-HEP exhibited a pattern for fentanyl metabolite formation similar to that observed in vivo. In addition, the phase I and II drug-metabolizing enzyme activities of HepaRG, h-iPS-HEP, liver-humanized mouse-derived hepatocytes (PXB-cellsTM), and human primary hepatocytes were evaluated and compared. HepaRG showed high phase I and II drug metabolism activities; however, the CYP2D6 activity in these cells was quite low, and therefore h-iPS-HEP lacked O-methylation and conjugation activities. PXB-cells provided optimal results, i.e., these cells are extremely easy to use, and they possess higher phase I and II drug-metabolizing enzyme activities than the other cells tested. Although PXB-cells are contaminated with mouse-derived cells up to a concentration of several percent, this cell system appears to be promising for the prediction of in vivo human metabolism of new drugs of abuse.


Assuntos
Canabinoides/metabolismo , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Animais , Linhagem Celular , Citocromo P-450 CYP2D6/metabolismo , Fentanila/metabolismo , Humanos , Metilação , Camundongos
5.
Biol Pharm Bull ; 42(4): 623-630, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30930421

RESUMO

The metabolism of butyrylfentanyl, a new designer drug, was investigated using fresh human hepatocytes isolated from a liver-humanized mouse model. In the culture medium of hepatocytes incubated with butyrylfentanyl, the desphenethylated metabolite (nor-butyrylfentanyl), ω-hydroxy-butyrylfentanyl, (ω-1)-hydroxy-butyrylfentanyl, 4'-hydroxy-butyrylfentanyl, ß-hydroxy-butyrylfentanyl, 4'-hydroxy-3'-methoxy-butyrylfentanyl, and ω-carboxy-fentanyl were identified as the metabolites of butyrylfentanyl. Each metabolite was definitively identified by comparing the analytical data with those of authentic standards. The amount of the main metabolite, nor-butyrylfentanyl, reached 37% of the initial amount of butyrylfentanyl at 48 h. ω-Hydroxy-butyrylfentanyl and (ω-1)-hydroxy-butyrylfentanyl, formed by hydroxylation at the N-butyryl group of butyrylfentanyl, were the second and third largest metabolites, respectively. The majority of 4'-hydroxy-butyrylfentanyl and 4'-hydroxy-3'-methoxy-butyrylfentanyl was considered to be conjugated. CYP reaction phenotyping for butyrylfentanyl using human liver microsomes and various anti-CYP antibodies revealed that CYP3A4 was involved in the formation of nor-butyrylfentanyl, (ω-1)-hydroxy-butyrylfentanyl, and ß-hydroxy-butyrylfentanyl. In contrast, CYP2D6 was involved in the formation of ω-hydroxy-butyrylfentanyl.


Assuntos
Fentanila/análogos & derivados , Hepatócitos/metabolismo , Drogas Ilícitas/metabolismo , Células Cultivadas , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Fentanila/metabolismo , Humanos , Microssomos Hepáticos/metabolismo , Padrões de Referência
6.
Analyst ; 144(6): 2158-2165, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30747180

RESUMO

Sensitive detection of drugs using a method with high qualification capability is important for forensic drug analysis. Vibrational spectroscopy is a powerful screening technique because it can provide detailed structural information of the compounds included in samples with simple experimental protocols. Among various spectroscopic techniques, surface enhanced Raman scattering (SERS) spectroscopy has attracted enormous attention owing to its ultra-high sensitivity. In this study, we developed a method for rapid detection of hypnotics using SERS with gold nanoparticle co-aggregation in a wet system. The developed method required a simple analytical protocol. This enabled rapid analysis with high stability and repeatability. We analyzed various hypnotics (19 types including benzodiazepines and nonbenzodiazepines) to investigate the structure-spectrum relationship. As a proof of concept for application to real crime samples, simulated spiked beverages containing one hypnotic (etizolam, flunitrazepam, zolpidem, or zopiclone) were analyzed. Diluting the beverage samples decreased the matrix effect and allowed for detection of these hypnotics. Except for flunitrazepam, strong signals were observed for all hypnotics, and the estimated lower limit of detection was 50 ppm in apple drink. The developed approach is a rapid method for screening analysis of hypnotics with low sample requirements.

7.
Int J Legal Med ; 133(1): 117-122, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30242469

RESUMO

During investigations of unnatural death, the time of death is generally estimated using anatomical examinations. However, it can be difficult to accurately determine the day of death, because postmortem changes in the body tissues can be greatly affected by the circumstances of the location of the corpse. We recently developed a method to estimate the day of drug ingestion, using micro-segmental hair analysis based on internal temporal markers (ITMs). In this method, ITMs are ingested at a specific time interval before hair collection to mark timescales within individual hair strands. A single hair strand is segmented at 0.4-mm intervals, corresponding to average daily hair growth. The day of drug ingestion is eventually estimated by calculating the distances between segments containing the drug and ITMs in a hair strand. In the present study, the method was applied to estimate the day of death. A corpse was discovered with a documented medical history of lidocaine administration for surgery 57 days before the discovery. Micro-segmental analysis of a hair plucked from the corpse was performed using lidocaine as an ITM. Lidocaine was detected at specific regions in the hair strands. The day of death was estimated using the known surgery day, the distance from the hair root to the lidocaine peak in the hair strand, and the average hair growth rate. The novel estimation method using a hair enabled us to narrow the estimated time range of death up to the day of death, unlike the conventional anatomical examination. The micro-segmental hair analysis based on drug use history can be extremely helpful in determining the time of an unnatural death.


Assuntos
Anestésicos Locais/análise , Toxicologia Forense/métodos , Cabelo/química , Lidocaína/análise , Mudanças Depois da Morte , Cabelo/crescimento & desenvolvimento , Humanos
8.
Forensic Sci Int ; 291: 68-75, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30149281

RESUMO

In recent years, the need for analyzing cannabis DNA has increased in order to accommodate the various types of cannabis samples encountered in forensic investigation. This study was aimed to establish a simple and accurate cannabis DNA detection system using DNA chromatography. Two chromatography chip systems with different features were successfully developed. One system (the "four-line version") involves tetraplex PCR amplification, which could be used to detect cannabis DNA and distinguish between drug-type and fiber-type cannabis using the tetrahydrocannabinolic acid synthase gene sequence. The other system was the "three-line version" with triplex amplification, which was specialized to distinguish cannabis from other plants, and had a sensitivity (10fg DNA/reaction) that was 100 times greater than the four-line version. In both versions, no false positives were observed for 60 medicinal plants, and accurate detection could be performed for several simulated forensic samples such as cannabis leaves, buds, stems, roots, seeds, resin, and cannabis leaves blended 1/100 in tobacco. Detection could be performed by the naked eye and only a thermal cycler was required for operation. Thus, DNA chromatography systems for cannabis detection are expected to contribute to the analysis of cannabis DNA in forensic chemistry laboratories without extensive equipment.


Assuntos
Cannabis/genética , Cromatografia/métodos , DNA de Plantas , Primers do DNA , Toxicologia Forense , Limite de Detecção , Reação em Cadeia da Polimerase
9.
Forensic Toxicol ; 36(2): 467-475, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29963210

RESUMO

Purpose: The usefulness of hepatocytes isolated from a liver-humanized mouse (PXB-cells) as a model in vitro system for the prediction of the in vivo metabolism of new drugs of abuse was evaluated. Methods: For the drug metabolism study, fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of fentanyl, were selected as model drugs. PXB-cells were cultured with the drug for 24-48 h and then the media were collected and analyzed by liquid chromatography/mass spectrometry after deproteinization with acetonitrile. Results: The main metabolite formed from fentanyl by PXB-cells was the desphenethylated metabolite (nor-fentanyl), and the other major metabolites formed were 4'-hydroxy-fentanyl, ß-hydroxy-fentanyl and (ω-1)-hydroxy-fentanyl. ω-Hydroxy-fentanyl and 4'-hydroxy-3'-methoxy-fentanyl were the minor metabolites. Similar results were obtained for acetylfentanyl. The metabolite profile of fentanyl in PXB-cells was consistent with the in vivo metabolite profile of fentanyl reported previously. Most of the 4'-hydroxy- and 4'-hydroxy-3'-methoxy-metabolites of fentanyl and acetylfentanyl were conjugated in PXB-cells, indicating that PXB-cells had high conjugation enzyme activities. From experiments using human liver microsomes and anti-CYP antibodies, it was revealed that CYP3A4 was involved in the production of nor-fentanyl, ß-hydroxy-fentanyl and (ω-1)-hydroxy-fentanyl, while CYP2D6 was partially involved in the production of 4'-hydroxy-fentanyl. Conclusions: Our results indicated that PXB-cells have high activities of phase I and phase II drug-metabolizing-enzymes, can be stably supplied, and are easy to use; thus, PXB-cells are highly useful for the prediction of the in vivo metabolism of drugs of abuse.

10.
Forensic Sci Int ; 287: 176-182, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29677592

RESUMO

In recent years, analysis of cannabis DNA has been increasingly used in forensic drug tests. However, in the case of cannabis resin, a processed marijuana product, complicated procedures are required for the extraction of clean DNA, as the presence of various impurities inhibits PCR amplification. Therefore, in this study, we attempted to identify the factors that would allow quick and simple DNA extraction from cannabis resin with a commercially available kit. We also constructed a simple assay system for comparing relative amplification efficiencies by end-point PCR and used it to evaluate the purity of the obtained DNA solutions. For extraction with a kit that contains a silica column, reducing the starting amount of resin, using the residue remaining after methanol extraction, dilution of the final solution, extraction with an equal amount of powdered activated carbon or an excess amount of polyvinylpolypyrrolidone, and the addition of an appropriate amount of polyvinylpyrrolidone to the solution after extraction were effective measures that improved amplification efficiency. Furthermore, the use of the most rapid alkaline extraction kit combined with the addition of powdered activated carbon allowed obtaining DNA solutions with sufficient amplification efficiency in about 10min. These findings should be useful for routine DNA analysis of cannabis resin during forensic examination.


Assuntos
Cannabis/genética , DNA de Plantas/genética , Reação em Cadeia da Polimerase , Toxicologia Forense/métodos
11.
Forensic Sci Int ; 288: 23-28, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29705586

RESUMO

Sleeping aids are often abused in the commission of drug-facilitated crimes. Generally, there is little evidence that a victim ingested a spiked drink unknowingly because the unconscious victim cannot report the situation to the police immediately after the crime occurred. Although conventional segmental hair analysis can estimate the number of months since a targeted drug was ingested, this analysis cannot determine the specific day of ingestion. We recently developed a method of micro-segmental hair analysis using internal temporal markers (ITMs) to estimate the day of drug ingestion. This method was based on volunteer ingestion of ITMs to determine a timescale within individual hair strands, by segmenting a single hair strand at 0.4-mm intervals, corresponding to daily hair growth. This study assessed the ability of this method to estimate the day of ingestion of an over-the-counter sleeping aid, diphenhydramine, which can be easily abused. To model ingestion of a diphenhydramine-spiked drink unknowingly, each subject ingested a dose of diphenhydramine, followed by ingestion of two doses of the ITM, chlorpheniramine, 14days apart. Several hair strands were collected from each subject's scalp several weeks after the second ITM ingestion. Diphenhydramine and ITM were detected at specific regions within individual hair strands. The day of diphenhydramine ingestion was estimated from the distances between the regions and the days of ITM ingestion. The error between estimated and actual ingestion day ranged from -0.1 to 1.9days regardless of subjects and hair collection times. The total time required for micro-segmental analysis of 96 hair segments (hair length: 3.84cm) was approximately 2days and the cost was almost the same as in general drug analysis. This procedure may be applicable to the investigation of crimes facilitated by various drugs.


Assuntos
Crime , Difenidramina/análise , Medicina Legal/métodos , Cabelo/química , Medicamentos Indutores do Sono/análise , Detecção do Abuso de Substâncias/métodos , Bebidas , Biomarcadores/análise , Clorfeniramina/análise , Efedrina/análogos & derivados , Efedrina/análise , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Fatores de Tempo
12.
Biol Pharm Bull ; 41(1): 106-114, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29311471

RESUMO

To evaluate the capability of human-induced pluripotent stem cell-derived hepatocytes (h-iPS-HEP) in drug metabolism, the profiles of the metabolites of fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of fentanyl, in the cells were determined and analyzed. Commercially available h-iPS-HEP were incubated with fentanyl or acetylfentanyl for 24 or 48 h. After enzymatic hydrolysis, the medium was deproteinized with acetonitrile, then analyzed by LC/MS. Desphenethylated metabolites and some hydroxylated metabolites, including 4'-hydroxy-fentanyl and ß-hydroxy-fentanyl, were detected as metabolites of fentanyl and acetylfentanyl in the medium. The main metabolite of fentanyl with h-iPS-HEP was the desphenethylated metabolite, which was in agreement with in vivo results. These results suggest that h-iPS-HEP may be useful as a tool for investigating drug metabolism.


Assuntos
Analgésicos Opioides/metabolismo , Fentanila/análogos & derivados , Hepatócitos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Analgésicos Opioides/química , Biotransformação , Técnicas de Cultura de Células , Células Cultivadas , Cromatografia Líquida , Meios de Cultura , Fentanila/química , Fentanila/metabolismo , Hepatócitos/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Estrutura Molecular , Espectrometria de Massas em Tandem
13.
Forensic Sci Int ; 282: 86-91, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29174515

RESUMO

Methods to quickly purify methamphetamine hydrochloride from the cutting agent dimethyl sulfone for subsequent identification of confiscated crystalline samples using infrared absorption spectroscopy were compared and evaluated. Although sequential solvation and reprecipitation methods were simple, spectral contamination from dimethyl sulfone was inevitable and might affect the interpretation of the spectra. In addition, methamphetamine hydrochloride and dimethyl sulfone could form a solid solution because of solvation of both crystals into a single solution layer. By contrast, sublimation was an effective method for separation of methamphetamine hydrochloride and dimethyl sulfone. Sublimation combined with infrared absorption spectroscopy enabled rapid identification of crystalline methamphetamine hydrochloride.

14.
Drug Test Anal ; 10(4): 750-760, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28809091

RESUMO

Segmental hair analysis is used to estimate the time of drug intake at monthly precision in drug-related crimes. Previously, we advanced this analytical method to specify the day of drug intake by cutting a strand of hair into 0.4-mm segments, which correspond to daily hair growth. Herein, we investigated the distributions of 7 compounds in a strand of hair using micro-segmental analysis. Several strands of hair were collected 33.1-229.4 days after subjects were administered 4 pharmaceutical products that contained 10 drugs in single doses within 32 hours. The administered drugs and resulting metabolites were extracted from 0.4-mm hair segments and quantified using liquid chromatography-tandem mass spectrometry. Acidic and neutral compounds were detected at low amounts in any of the hair segments analyzed. Epinastine, fexofenadine, dihydrocodeine, chlorpheniramine, and the chlorpheniramine metabolite, desmethylchlorpheniramine each was localized to 2 regions within a strand of hair. By contrast, methylephedrine and its metabolite, ephedrine, each was localized to only a region. Among 20 individual strands of hair associated with different subjects and head regions, few differences in the shapes of drug concentration-hair segment curves for each compound were detected. Our data indicated that 2 mechanisms for drug uptake into hair can operate depending on drug properties and that co-administered drugs can be localized to different regions in a strand of hair. Micro-segmental analysis may aid in the identification of the day of drug intake and help to elucidate the mechanisms of drug uptake into hair.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cabelo/química , Preparações Farmacêuticas/análise , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos , Toxicologia Forense/métodos , Humanos , Limite de Detecção
15.
J Forensic Sci ; 62(6): 1472-1478, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28649754

RESUMO

The cis and trans isomers of 3-methylfentanyl and its three analogs were chemically synthesized, and these compounds were characterized and differentiated by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), and nuclear magnetic resonance (NMR) spectroscopy. The cis and trans isomers of the 3-methylfentanyl analogs were completely separated by GC/MS. Although the high temperature of the GC injection port caused thermal degradation of ß-hydroxy-3-methylfentanyl, the degradation was completely suppressed by trimethylsilyl derivatization. The isomers were also well separated by LC/MS on an octadecylsilyl column with 10 mM ammonium acetate and methanol as the mobile phase. The proton NMR signals were split when the hydrochloride salts of the 3-methylfentanyl analogs were dissolved in deuterated chloroform because stereoisomers were formed by the coordination of the hydrochloride proton to the nitrogen of the piperidine ring of the 3-methylfentanyl analogs.

16.
Forensic Sci Int ; 273: 39-44, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28213186

RESUMO

The enantiomers of methamphetamine were differentiated by supercritical fluid chromatography (SFC) with an enantioselective cellulose-based packed column. The optimization of the chromatographic conditions was achieved by changing column temperature, co-solvent proportion, additive concentration, flow rate and back pressure. In particular, the additive concentration crucially changed the resolution between the enantiomers. After determining the optimized conditions, the enantiomers of methamphetamine were successfully separated. The analytical precision, accuracy and limit of detection were checked by using the authentic standard and seized real samples. We believe that chiral SFC is a promising method for enantioseparation of forensic samples.

17.
Forensic Sci Int ; 270: 267-274, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27836413

RESUMO

The Scott test, widely used as the field test for cocaine, is performed in three steps. If a sample contains cocaine, blue precipitates appear in step 1, the precipitates are dissolved and the solution turns pink in step 2, and the lower layer turns blue in step 3. However, some pyrrolidine-type cathinones produce cocaine-like results when tested, necessitating modification of the test procedure. Filtration of the second-step mixture weakened the blue color in step 3; however, the blue color did not completely disappear. Adding the Chen-Kao reagent to the test procedure enhanced the differentiation: when the reagent was added to cocaine, the solution was initially turbid, but then became clear over time; its addition to cathinones resulted in turquoise or light sky-blue precipitation. These results indicated that the Chen-Kao test was useful for exclusion of cathinones. A combination of the modified Scott test and the Chen-Kao test was successfully applied to the forensic samples containing cocaine or pyrrolidine-type cathinones. In conclusion, a combination of these tests will be the useful field-test procedure for cocaine.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Cocaína/isolamento & purificação , Entorpecentes/isolamento & purificação , Detecção do Abuso de Substâncias/métodos , Humanos , Indicadores e Reagentes
18.
J Forensic Sci ; 62(2): 488-492, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27874182

RESUMO

In the study reported here, two glucuronic acid-conjugated metabolites of 4-bromo-2,5-dimethoxyphenethylamine (2C-B)-a ring-substituted psychoactive phenethylamine-were chemically synthesized for the first time and a method for analyzing them in urine was developed. ß-D-Glucuronide of 4-bromo-2,5-dimethoxyphenylethylalcohol was successfully synthesized using methyl 2,3,4-tri-Ο-acetyl-1-O-(trichloroacetimidoyl)-α-D-glucuronate as a glucuronyl donor and boron trifluoride diethylether complex as a Lewis acid catalyst. ß-D-Glucuronide of 4-bromo-2,5-dimethoxyphenylacetic acid was synthesized by condensing 4-bromo-2,5-dimethoxyphenylacetic acid and benzyl D-glucuronate followed by benzyl group deprotection based on catalytic hydrogenation. Two glucuronic acid-conjugated metabolites of 2C-B in urine were qualitatively and semiquantitatively evaluated via direct liquid chromatography/mass spectrometry (LC/MS) analysis of a diluted urine sample. The simple method proposed is expected to be useful for studying the metabolic fate of 2C-B.


Assuntos
Dimetoxifeniletilamina/análogos & derivados , Ácido Glucurônico/síntese química , Psicotrópicos/síntese química , Psicotrópicos/urina , Adulto , Cromatografia Líquida , Dimetoxifeniletilamina/síntese química , Dimetoxifeniletilamina/urina , Glucuronídeos/síntese química , Humanos , Masculino , Espectrometria de Massas , Detecção do Abuso de Substâncias
19.
Drug Test Anal ; 9(4): 571-577, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27341179

RESUMO

Hair and nails are often used to prove long-term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time-courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12 months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Toxicologia Forense/métodos , Cabelo/química , Unhas/química , Preparações Farmacêuticas/análise , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Humanos , Limite de Detecção , Preparações Farmacêuticas/administração & dosagem , Detecção do Abuso de Substâncias/métodos
20.
Drug Test Anal ; 9(3): 389-398, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27383263

RESUMO

Chromatographic differentiation of the ring-substituted regioisomers of amphetamine (AMP) and methamphetamine (MA) was performed by supercritical fluid chromatography (SFC). The behaviour of the retention against the changes of column temperature and co-solvent proportion was studied. The obtained information facilitated the optimization of the each regioisomer. As a result, 2-, 3-, and 4-ring-substituted analogues of AMP and MA with methyl, methoxy, fluoro, chloro, and bromo groups were separated, generally within 6 min. In addition, we found that the separation pattern of the examined regioisomers was classified into two, which depended on the electron donating/withdrawing effect of the substituent. Our results indicate that SFC could be used in forensic drug analysis for fast, reliable identification of structurally similar drugs of abuse. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Anfetamina/química , Estimulantes do Sistema Nervoso Central/química , Metanfetamina/química , Anfetamina/isolamento & purificação , Estimulantes do Sistema Nervoso Central/isolamento & purificação , Cromatografia com Fluido Supercrítico , Metanfetamina/isolamento & purificação , Solventes , Estereoisomerismo
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