著者

松本 謙吾 掛橋 秀直 鎌田 寛恵 志摩 典明 鎌田 徹 片木 宗弘 西岡 裕

出版者

日本法科学技術学会

雑誌

日本法科学技術学会誌 (ISSN:18801323)

巻号頁・発行日

vol.28, no.2, pp.103-112, 2023 (Released:2023-07-31)

参考文献数

16

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Cannabidiol (CBD), an uncontrolled cannabinoid in marijuana, is readily converted to the controlled Δ9- and Δ8-THCs under acidic conditions. In this study, we monitored the time-course conversion of CBD into the two THCs using easily available acids and solvents by gas chromatography-mass spectrometry. Placing CBD (3.3 mg/mL) in 4.2 mM sulfuric acid-glacial acetic acid solution at room temperature resulted in the production of Δ9-Tetrahydrocannabinol (Δ9-THC) after 3 hours, followed by Δ8-THC after 96 hours. The conversion continued, and their relative abundance was Δ9-THC>CBD>Δ8-THC after 192 hours. Elevating the sulfuric acid concentration to 42 mM promoted the conversion to where CBD depleted in 3 hours, Δ9-THC production peaked (and started to decline) at 12 hours, and Δ8-THC became the major constituent at 100 hours. Replacing sulfuric acid with muriatic acid showed the similar time-course conversion. The THCs/CBD ratio varies under acidic conditions; this ratio can be used as an indicator for identifying the product lots of liquid drugs containing THCs converted from CBD. Ethanol, alternative solvent to glacial acetic acid, kept CBD unchanged with 42 mM sulfuric acid for 192 hours at room temperature, but conversion into Δ9-THC was observed after 6 hours when heated at 70℃. Without an acid catalyst, CBD was stable under heating cycles from 60℃ to 130℃ in an electric vaporizer. Thus, the unintentional production of THCs seems unlikely only by heating a commercial CBD product. The CBD-to-THCs conversion also yielded several by-products. Among them, possible Δ8-iso-THC was detected under all 12 combination conditions (two catalytic acids and six solvents) investigated in this study. Additionally, the use of alcohol solvents produced alcohol adducts of the THCs. Detection of by-products therefore can provide more solid information for identifying the product lots and estimating the condition of CBD conversion.

著者

鎌田 徹 片木 宗弘 中西 啓子 財津 桂 志摩 典明 鎌田 寛恵 三木 昭宏 土橋 均

出版者

日本法科学技術学会

雑誌

日本法科学技術学会誌 (ISSN:18801323)

巻号頁・発行日

vol.15, no.1, pp.15-23, 2010 (Released:2010-02-27)

参考文献数

18

被引用文献数

3 3

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The metabolism and urinary excretion of N-hydroxy-3,4-methylenedioxymethamphetamine (N-OH MDMA), a newly banned narcotic in Japan, were explored to confirm biotransformation of N-OH MDMA to 3,4-methylenedioxymethamphetamine (MDMA) and to discriminate between N-OH MDMA and MDMA intake in forensic urine analysis. The in vitro and the in vivo experiences were performed with human liver S9 and rats, respectively, and the resultant products or metabolites were determined using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry.   In both the in vitro and the in vivo experiences, MDMA and 3,4-methylenedioxyamphetamine (MDA) were detected, and the MDA levels exceeded the MDMA levels throughout the entire periods except for during 3 h after administration to the rats. This suggests the existence of the metabolic pathway(s) from N-OH MDMA to MDA not via MDMA. In urine samples from the administered rats parent N-OH MDMA and its demethylated metabolite N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) with very low levels during short period after administration (≤6 h) were detected. The ratios of the urinary MDA/MDMA levels for N-OH MDMA-administered rats were higher than those for MDMA-administered rats. In addition, the determination of urinary diastereomers of glucuronidated 4-hydroxy-3-methoxymethamphetamine (HMMA), MDMA metabolite, revealed that the relative peak intensity of l-HMMA-glucuronide to d-HMMA-glucuronide was higher in the case of N-OH MDMA-administration than in the case of MDMA-administration.   Detection of MDMA in both the in vitro and the in vivo experiences suggests that N-OH MDMA intake will result in MDMA excretion also in human urine. To discriminate between N-OH MDMA and MDMA intake the following view points would be applicable in urine analysis: 1) detection of N-OH MDMA and/or N-OH MDA, 2) MDA/MDMA ratio, and 3) peak intensities of diastereomeric HMMA-glucuronides.

著者

財津 桂 片木 宗弘 中西 啓子 志摩 典明 鎌田 寛恵 鎌田 徹 西岡 裕 三木 昭宏 辰野 道昭 岩村 樹憲 佐藤 貴子 土橋 均 鈴木 廣一

出版者

日本法科学技術学会

雑誌

日本法科学技術学会誌 (ISSN:18801323)

巻号頁・発行日

vol.16, no.2, pp.73-90, 2011 (Released:2011-08-12)

参考文献数

31

被引用文献数

4 3

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Comprehensive analytical method to identify 11 kinds of synthetic cannabinoids has been investigated by thin layer chromatography (TLC), gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). The analytes used in this study have already been detected from various herbal-type designer drugs: 8 kinds of aminoalkylindoles (AAIs) (JWH-015, JWH-018, JWH-073, JWH-081, JWH-200, JWH-250, JWH-251 and JWH-398), two kinds of cyclohexylphenols (CPs) (CP 47,497 and Cannabicyclohexanol), and a Δ9-tetrahydrocannabinol analog (HU-210).   Although specific color changes were observed for the cannabinoids using Marquis reagent, identification of each analyte based on Rf values was difficult to be obtained by TLC.   On the other hand, GC/MS and LC/MS/MS were appropriate for their qualitative analyses because of their chromatographic and mass spectral differentiation. A semi-polar capillary column DB-5MS showed the best separation and retention properties of the targeted cannabinoids among the tested GC column phases. Also, characteristic fragment ions were observed in each electron ionization-mass spectrum. The observed fragment ions were mainly derived from α-cleavage of ketone and α-cleavage of amine for AAIs, simple cleavage for CPs, and McLafferty rearrangements for HU-210.   Based on the ionization efficiency of the target analytes using LC/MS/MS, electrospray ionization positive mode was selected for AAIs, and negative mode for CPs and HU-210. All analytes were completely separated by gradient elution of ammonium formate aqueous solution-acetonitrile mobile phase on a C18 (ODS) separation column. In addition, characteristic fragment ions were observed in product ion spectra of AAIs and second generation product ion spectra of CPs and HU-210, enabling reliable confirmation.   These results provide useful information not only for simultaneous analyses of the targeted cannabinoids but also for structural assignment of future cannabimimetic compounds that may appear in the illicit drug market.

著者

掛橋 秀直 志摩 典明 鎌田 寛恵 松田 駿太朗 中野 史保子 和田 美暁 佐々木 啓子 鎌田 徹 西岡 裕 財津 桂 土橋 均 三木 昭宏 片木 宗弘

出版者

日本法科学技術学会

雑誌

日本法科学技術学会誌 (ISSN:18801323)

巻号頁・発行日

vol.22, no.2, pp.77-90, 2017 (Released:2017-07-27)

参考文献数

26

被引用文献数

1

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Three analogues of 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PVP), 1-(4-fluorophenyl)-2-(pyrolidin-1-yl)pentan-1-one (4F-α-PVP), 1-(4-methoxyphenyl)-2-(pyrrolidin-1-yl)pentan-1-one (4MeO-α-PVP) and 2-(pyrrolidin-1-yl)-1-(thiophen-2-yl)pentan-1-one (α-PVT), and their metabolites were determined in users' urine by liquid chromatography-tandem mass spectrometry using newly synthesized authentic standards. The identified metabolites indicated that metabolic pathways of three α-PVP analogues include the reduction of the carbonyl group to the corresponding alcohols and the oxidation of the pyrrolidine ring to the corresponding pyrrolidone, and 4MeO-α-PVP and α-PVT have additional metabolic pathways of the O-demethylation and the oxidation of thienyl group respectively. The quantitative analyses of the urinary metabolites suggested that the main metabolic pathways of these α-pyrrolidinophenones (PPs) derivatives could vary largely depending on the aromatic rings or substituent groups on the aromatic ring of PPs.

著者

掛橋 秀直 鎌田 寛恵 石川 亜香里 浅井 龍太郎 新田 篤志 和田 美暁 中野 史保子 松田 駿太朗 佐々木 啓子 志摩 典明 鎌田 徹 西岡 裕 三木 昭宏 片木 宗弘

出版者

日本法科学技術学会

雑誌

日本法科学技術学会誌 (ISSN:18801323)

巻号頁・発行日

vol.24, no.1, pp.73-78, 2019 (Released:2019-01-31)

参考文献数

6

被引用文献数

2

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N-tert-Butoxycarbonyl-methamphetamine (t-BOCMA), a tert-butoxycarbonyl (t-BOC) derivative of methamphetamine (MA), which has recently been reported in several countries, was seized for the first time in Japan in 2017. It deprotected easily in an acidic condition to result in an illicit MA, and recently became a newly designated drug of the Pharmaceutical and Medical Device Act. For drug enforcement, the information of its properties was, therefore, strongly demanded. In this study, we synthesized the t-BOCMA standard, acquired various analytical data, and demonstrated its conversion to MA in high yield in the relatively moderate acidic condition (5% HCl methanol solution, 50℃). Also, the stability of t-BOCMA in simulated gastric juice (0.08 M HCl, 37℃) was explored by using GC/MS. As the result, 19% of t-BOCMA remained even after 120 min incubation, and the T1/2 was calculated to be 50 min. These suggest that the orally ingested t-BOCMA would be absorbed into blood in some degree without conversion to MA.

著者

松田 駿太朗 片木 宗弘 西岡 裕 鎌田 寛恵 佐々木 啓子 志摩 典明 鎌田 徹 三木 昭宏 辰野 道昭 財津 桂 坪井 健人 土橋 均 鈴木 廣一

出版者

日本法科学技術学会

雑誌

日本法科学技術学会誌 (ISSN:18801323)

巻号頁・発行日

vol.19, no.2, pp.77-89, 2014 (Released:2014-07-30)

参考文献数

12

被引用文献数

12 18

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Cathinone-type designer drugs are a newly-encountered drug family that has a β-ketophenethylamine skeleton. Recently, the abuse of these drugs has been increasingly common among young adults, and this has caused a serious social problem in many countries. Many of those drugs have become regulated by the Pharmaceutical Affairs Act, and some of them were later banned by the Narcotics and Psychotropics Control Act in Japan, depending on their structures. In this paper, a total of 98 standards of cathinone-type designer drugs were synthesized, and their EI-mass spectra were acquired by GC/MS, with and without trifluoroacetylation. For their free bases, a major fragment ion formed from the α-cleavage of the amine nitrogen was commonly observed. Also, a small fragment ion generated by the α-cleavage of the carbonyl group, followed by the elimination of CO was detectable. For the analogs having an N-alkyl chain longer than methyl group and/or the alkyl side-chain longer than methyl group, a characteristic ion formed from the α-cleavage of the amine nitrogen, followed by the elimination of the olefin moiety was observed. For the trifluoroacetyl derivatives, the intensity of fragment ion formed from the α-cleavage of carbonyl group significantly increased, while that of the fragment ion generated from the α-cleavage of nitrogen decreased, when compared with those of free bases. Also, the ion at m/z 110 was specifically observed for the cathinone analogs having a methylamino group. Those typical fragmentation patterns revealed by analyzing a series of analogs provide useful information for the characterization of cathinone-type designer drugs.

著者

財津 桂 片木 宗弘 中西 啓子 鎌田 徹 志摩 典明 鎌田 寛恵 石丸(飯尾) 麗子 岩室 嘉晃 地中 啓 高山 成明 三木 昭宏 土橋 均

出版者

日本法科学技術学会

雑誌

日本法科学技術学会誌 (ISSN:18801323)

巻号頁・発行日

vol.15, no.1, pp.25-37, 2010 (Released:2010-02-27)

参考文献数

17

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Comprehensive analytical procedures for the unequivocal determination of a newly encountered drug “N-hydroxy-3,4-methylenedioxymethamphetamine (N-OH-MDMA)”, which is expected to be chemically unstable and thermally decomposed to MDMA during the analyses, have been investigated by using various qualitative analyses including color tests, thin layer chromatography (TLC), infrared spectroscopy (IR), gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), liquid chromatography/tandem mass spectrometry (LC/MS/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Stability of N-OH-MDMA in aqueous solutions with several pH values and its recovery throughout the liquid-liquid extraction with ethyl acetate (EA) were also examined. Both the color tests and TLC suggested that Simon's reagent and Rf values were helpful for discrimination of N-OH-MDMA and MDMA. The IR spectra of both N-OH-MDMA hydrochloride and MDMA hydrochloride showed a sufficient difference, and the IR spectrum of N-OH-MDMA oxalate, could be identified by some of its specific peaks. GC/MS has demonstrated that both free base and its trifluoroacetyl derivative were easily decomposed to MDMA and other related products in the GC injection port, though trimethylsilyl derivatization prevented its pyrolytic disproportionation to MDMA. On the other hand, LC/MS, LC/MS/MS and CE/MS procedures were found to be reliable techniques for determination of N-OH-MDMA without its thermal and chemical decomposition. Based on the stability studies, N-OH-MDMA proved stable in acid solution, while it was expected to be transformed to isoquinoline-type compounds in neutral solution and readily decomposed to its relevant oxime in alkaline solution. Since no difference of the extraction efficiencies with EA was observed under the neutral and alkaline conditions, the extraction should be done under neutral condition to minimize its decomposition.