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

志摩 典明 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

pp.r022, (Released:2021-07-16)

参考文献数

65

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Increasing numbers of drug-facilitated sexual assaults (DFSAs) have been reported recently and have become a social concern. In DFSAs, biological specimens (urine, blood, and hair) are analyzed to prove the victim's drug exposure, which can lead to proof of the sexual crime. Hair is the only specimen that can provide firm evidence of drug ingestion in cases of long delays (more than a week) in reporting the crime. Furthermore, detailed sectional hair analysis of a single hair strand enables to estimate the victim's drug-use history (date and amount of intake). Several recent studies have demonstrated high-sensitivity methods using mass spectrometry to detect sub-pg/mg concentrations of hypnotics in hair, and additionally illustrated the incorporation pathways of drugs and detailed distribution patterns in the hair after intake. Based on these findings, hair testing for hypnotics has been put to practical applications since 2016. In this paper, we review the practical concepts and usefulness of hair testing for hypnotics while introducing the current situation of DFSAs.

著者

志摩 典明 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.26, no.2, pp.137-157, 2021 (Released:2021-07-31)

参考文献数

65

---

Increasing numbers of drug-facilitated sexual assaults (DFSAs) have been reported recently and have become a social concern. In DFSAs, biological specimens (urine, blood, and hair) are analyzed to prove the victim's drug exposure, which can lead to proof of the sexual crime. Hair is the only specimen that can provide firm evidence of drug ingestion in cases of long delays (more than a week) in reporting the crime. Furthermore, detailed sectional hair analysis of a single hair strand enables to estimate the victim's drug-use history (date and amount of intake). Several recent studies have demonstrated high-sensitivity methods using mass spectrometry to detect sub-pg/mg concentrations of hypnotics in hair, and additionally illustrated the incorporation pathways of drugs and detailed distribution patterns in the hair after intake. Based on these findings, hair testing for hypnotics has been put to practical applications since 2016. In this paper, we review the practical concepts and usefulness of hair testing for hypnotics while introducing the current situation of DFSAs.

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

志摩 典明

出版者

大阪府警察本部刑事部科学捜査研究所

雑誌

奨励研究

巻号頁・発行日

2012

---

強姦等の性犯罪では睡眠薬が悪用されることが多く、このようなケースでは、被害者を対象とした睡眠薬分析が、犯罪立件への強固な物的証拠となり得る。毛髪中に取り込まれた薬物は、半年~1年以上にわたって検出可能で、根本から一定間隔毎の分画分析によって、薬物摂取歴の推定も可能である。本研究では、覚せい剤等で確立された従来の液体クロマトグラフィータンデム質量分析法(LC-MS/MS)を睡眠薬用に最適化し、その有用性を検証する共に、従来法では頭髪を100~200本を必要とするため、検出限界の向上を試み、被害者の負担軽減を図った。更に、マトリックス支援レーザー脱離イオン化質量分析(MALDI-MS)によるイメージング分析法を検討し、1本の頭髪で、数日~一週間毎の摂取歴を特定できる分析法の開発を目指したものである。その結果、LC-MS/MSを用いて睡眠薬ゾルピデム単回摂取者の頭髪からゾルピデムの検出に成功した。さらに各種条件を検討することで、摂取後1ヶ月の頭髪1本からも検出することに成功した。本法を用いて、単回摂取により頭髪1本中に取り込まれる薬物量及び局在部位を検討するため、1本毎(n=15、毛根から0-2及び2-4cm)の定量分析を実施したところ、0-2cm分画からは1試料を除く全試料からゾルピデムが検出され、その濃度は27~63(42±12)pg/2-cmhair(n=14)で、比較的ばらつきがなく安定して頭髪中に取り込まれることが示唆された。また、MALDI-MSによる分析では、摂取後48時間以内の毛根から、睡眠薬としては初めて、ゾルピデムの検出に成功した。以上の結果は、日本法中毒学会(平成25年7月)で発表する予定である。

著者

浅井 龍太郎 鎌田 徹 新田 篤志 和田 美暁 掛橋 秀直 中野 史保子 松田 駿太朗 志摩 典明 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.43-48, 2019 (Released:2019-01-31)

参考文献数

18

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In order to expose substituted, cheated and faked urine specimens submitted for a drug test, a simple and highly sensitive screening method has been developed for the detection of urea in the specimens. This method uses the coloration of a piece of pH test paper which is wetted and set into the headspace of a sample vial containing “urine”, by absorbing NH3 gas generated by the urease reaction. The present method named, “Urease-Headspace method” (UHS method), was evaluated by applying it to various diluted or adulterated urine samples. The detection limit of urea in water was 2×10−4%, which was 100 times higher sensitivity compared with a conventional p-(dimethylamino)cinnamaldehyde (DAC) test. The UHS method was applicable even to deeply colored specimens such as bloody urine because the coloration occurs in the headspace of the sample vial. The UHS method quickly revealed the substituted specimens, e.g. water and green tea. Thus, the present UHS method will be effective for the validity determination of urine specimens, which is increasingly crucial in forensic drug examination.

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

志摩 典明 佐々木 啓子 鎌田 徹 三木 昭宏 片木 宗弘

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.139, no.5, pp.705-713, 2019-05-01 (Released:2019-05-01)

参考文献数

27

被引用文献数

2 2

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Hair testing for drugs has been used extensively in the field of forensics since the 1990s as a means of obtaining firm evidence of drug ingestion. In addition to its longer detection windows, hair is the only specimen that can provide chronological information on individual drug use. Illicit drugs and hypnotics account for the majority of substances involved in crimes; they are usually analyzed to prove an addictive use or an exposure to drugs in drug-facilitated crimes. The mechanism of drug incorporation into hair has been intensively investigated to properly interpret the results of hair analysis. However, the exact mechanism remains under much discussion, despite the growing application of hair tests. Recently, the authors have applied matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging and sectional hair analysis of 1-mm segments using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for single-strand hair, to investigate the incorporation pathways of drugs into hair. Time-course changes in drug distribution along single-strand hair suggest that the incorporation of drugs occurs in two regions of the hair root, the hair bulb and the upper part of hair root, and suggest that incorporation from the hair bulb continues for about 2 weeks. Distribution profiles of different drugs in hair additionally revealed that the main incorporation pathway varies (i.e., via the hair bulb or the upper part of hair root) depending on the properties of the drug/metabolite. These findings should be taken into account upon discussing individual drug-use history based on the results of hair analysis.

著者

志摩 典明

出版者

大阪府警察本部科学捜査研究所

雑誌

奨励研究

巻号頁・発行日

2019

---

睡眠薬は、強姦等の性犯罪・殺人等で悪用されることが多く、被害者を対象とした睡眠薬分析が、犯罪立件への強固な客観的証拠となる。特に、このような事案の鑑定においては、睡眠薬の検出に加えて、摂取時期や摂取量の特定が重要となる。本研究では、「薬物摂取量」の推定法について検証した。その結果、「薬物摂取量」と「頭皮近接部位から取り込まれた薬物量」は良好な比例関係を示しており、概ねの薬物摂取量を推定できることが示された。

著者

松田 駿太朗 掛橋 秀直 中野 史保子 志摩 典明 鎌田 徹 西岡 裕 三木 昭宏 坂本 雄紀 宮川 治彦 草野 麻衣子 財津 桂 土橋 均 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.109-121, 2017 (Released:2017-07-27)

参考文献数

13

被引用文献数

3

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In this study, we describe a rapid gas chromatography-tandem mass spectrometry (GC-MS/MS) analytical method that allows comprehensive detection and structural elucidation of synthetic cathinone-type designer drugs. Our proposed method consists of three simultaneous analytical procedures: 1) selective detection of the carbonyl group characteristic to each cathinone examined via selected reaction monitoring (SRM); and the determination of both 2) iminium cations and 3) substituted benzoyl cations generated via the α-cleavage of their corresponding amines and ketone moieties via product ion scanning, respectively.  One peak was detected in the SRM chromatogram for all cathinones examined in procedure 1), as well as the relevant single peaks in the total ion current chromatograms that resulted from procedures 2) and 3) at the same retention time. SRM of procedure 1) showed the transition of substituted benzoyl cations to substituted phenyl cations due to CO elimination, revealing the presence of carbonyl groups within the structures. Each product ion spectrum of the substituted benzoyl cation allowed for both determination of which group was substituted on the aromatic ring and differentiation between corresponding positional isomers for ethyl, methoxy and methylenedioxy substitution. However, identification of the substitution positions for the methyl, bromine and fluorine groups on the aromatic ring was difficult. On the other hand, differences between structural isomers in the product ion spectra of iminium cations were clearly identifiable, allowing for easy discrimination between isomers.

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 19

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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.