Structural Analysis and Characterization of 4-F-α-PVP Analog 4-F-3-Methyl-α- PVP Hydrochloride

doi:10.12116/j.issn.1004-5619.2021.311002

Abstract

Abstract:

Objective To identify 1-（4-fluorophenyl）-2-（1-pyrrolidinyl） pentan-1-one （4-F-α-PVP） analog 1-（4-fluoro-3-methyl phenyl）-2-（1-pyrrolidinyl） pentan-1-one （4-F-3-Methyl-α-PVP） hydrochloride without reference substance. Methods The direct-injection electron ionization-mass spectrometry （EI-MS）, GC-MS, electrospray ionization-high resolution mass spectrometry （ESI-HRMS）, ultra-high performance liquid chromatography-high resolution tandem mass spectrometry （UPLC-HRMS/MS）, nuclear magnetic resonance （NMR）, ion chromatography and Fourier transform infrared spectroscopy （FTIR） were integrated utilized to achieve the structural analysis and characterization of the unknown compound in the sample, and the cleavage mechanism of the fragment ions was deduced by EI-MS and UPLC-HRMS/MS. Results By analyzing the direct-injection EI-MS, GC-MS, ESI-HRMS and UPLC-HRMS/MS of the compound in the samples, it was concluded that the unknown compound was a structural analog of 4-F-α-PVP, possibly with one more methyl group in the benzene ring. According to the analysis results of ¹H-NMR and ¹³C-NMR, it was further proved that the methyl group is located at the 3-position of the benzene ring. Since the actual number of hydrogen in ¹H-NMR analysis was one more than 4-F-3-Methyl-α-PVP neutral molecule, it was inferred that the compound existed in the form of salt. Ion chromatography analysis results showed that the compound contained chlorine anion （content 11.14%-11.16%）, with the structural analysis of main functional group information by FTIR, the unknown compound was finally determined to be 4-F-3-Methyl-α-PVP hydrochloride. Conclusion A comprehensive method using EI-MS, GC-MS, ESI-HRMS, UPLC-HRMS/MS, NMR, ion chromatography and FTIR to identify 4-F-3-Methyl-α-PVP hydrochloride in samples is established, which will be helpful for the forensic science laboratory to identify this compound or other analog compounds.

Key words: forensic medicine, toxicological analysis, new psychoactive substance, high resolution mass spectrometry, nuclear magnetic resonance, 4-F-3-Methyl-α-PVP hydrochloride, structural analysis

CLC Number:

DF795.1

Hao-yang WANG, Jian WU, Qian ZHANG, Xin-feng MIN, Xiu-yan LIU, Yin-long GUO. Structural Analysis and Characterization of 4-F-α-PVP Analog 4-F-3-Methyl-α- PVP Hydrochloride[J]. Journal of Forensic Medicine, 2023, 39(2): 144-150.

Figures/Tables 10

References 13

1	沈敏. 新精神活性物质的应对与挑战[J].法医学杂志，2021，37（4）：453-458. doi：10.12116/j.issn.1004-5619.2021.310204 .
	SHEN M. The response and challenge of new psychoactive substances[J]. Fayixue Zazhi，2021，37（4）：453-458.
2	徐多麒，常林，向平，等. 论我国新精神活性物质监测评估系统完善[J].中国司法鉴定，2020（6）：60-65. doi：10.3969/j.issn.1671-2072.2020.06.009 .
	XU D Q， CHANG L， XIANG P， et al. On the improvement of the monitoring and evaluating system of new psychoactive substances in China[J]. Zhongguo Sifa Jianding，2020（6）：60-65.
3	MAJCHRZAK M， CELIŃSKI R， KUŚ P， et al. The newest cathinone derivatives as designer drugs： An analytical and toxicological review[J]. Forensic Toxicol，2018，36（1）：33-50. doi：10.1007/s11419-017-0385-6 .
4	KRAEMER M， BOEHMER A， MADEA B， et al. Death cases involving certain new psychoactive substances： A review of the literature[J]. Forensic Sci Int，2019，298：186-267. doi：10.1016/j.forsciint.2019. 02.021 .
5	黄志斌，蔡娟，林泽彬，等. 合成卡西酮类新精神活性物质对动物行为学影响的研究进展[J].法医学杂志，2021，37（4）：561-568. doi：10.12116/j.issn.1004-5619.2021.310406 .
	HUANG Z B， CAI J， LIN Z B， et al. Research progress on the effect of synthetic cathinones on animal behavior[J]. Fayixue Zazhi，2021，37（4）：561- 568.
6	中华人民共和国公安部，国家卫生和计划生育委员会，国家食品药品监督管理总局，国家禁毒委员会办公室. 关于印发《非药用类麻醉药品和精神药品列管办法》的通知：公通字〔2015〕27号[EB/OL].（2015-09-24）[2021-09-19].
	The Ministry of Public Security of the People’s Republic of China， National Health and Family Planning Commission of the People’s Republic of China， State Food and Drug Administration， China National Narcotic Control Committee. Notice on printing and distributing the Measures for Controlling Non-Medi-cinal Narcotic Drugs and Psychotropic Drugs： Gong Tong Zi 〔2015〕No. 27[EB/OL]. （2015-09-24）[2021-09-19].
7	中华人民共和国公安部. 法庭科学疑似毒品中α- PBP、α-PVP和4-F-α-PVP检验液相色谱和液相色谱-质谱法： [S].北京：中国标准出版社，2021.
	The Ministry of Public Security of the People’s Republic of China. Forensic sciences -- Examination methods for α-PBP， α-PVP and 4-F-α-PVP in suspected drugs -- LC and LC-MS： [S]. Beijing： China Standards Publishing Press，2021.
8	LIU C， JIA W， HUA Z， et al. Identification and analytical characterization of six synthetic cannabinoids NNL-3， 5F-NPB-22-7N， 5F-AKB-48-7N， 5F-EDMB-PINACA， EMB-FUBINACA， and EG-018[J]. Drug Test Anal，2017，9（8）：1251-1261. doi：10.1002/dta.2160 .
9	刘翠梅，花镇东，贾薇. 阿米雷司类似物4’-F-4-MAR的结构解析与表征[J].法医学杂志，2020，36（5）：677-681，687. doi：10.12116/j.issn.1004-5619.2020.05.013 .
	LIU C M， HUA Z D， JIA W. Structure analysis and characterization of aminorex analogue 4’-F-4-MAR[J]. Fayixue Zazhi，2020，36（5）：677-681，687.
10	王跨陡，袁晓亮，张玉荣，等. 合成大麻素类新精神活性物质4F-MDMB-BUTINACA和MDMB-4en-PINACA的检测[J].法医学杂志，2021，37（4）：505-510. doi：10.12116/j.issn.1004-5619.2020.300501 .
	WANG K D， YUAN X L， ZHANG Y R， et al. Identification of synthetic cannabinoid new psychoactive substances 4F-MDMB-BUTINACA and MDMB-4en-PINACA[J]. Fayixue Zazhi，2021，37（4）：505-510.
11	MOCHIZUKI A， ADACHI N， SHOJO H. Detection of 4-FMC， 4-MeO-α-PVP， 4-F-α-PVP， and PV8 in blood in a forensic case using liquid chromato-graphy-electrospray ionization linear ion trap mass spectrometry[J]. Forensic Sci Int，2021，325：110888. doi：10.1016/j.forsciint.2021.110888 .
12	DAVIDSON J T， PIACENTINO E L， SASIENE Z J， et al. Identification of novel fragmentation pathways and fragment ion structures in the tandem mass spectra of protonated synthetic cathinones[J]. Forensic Chem，2020，19：100245. doi：10.1016/j.forc.2020. 100245 .
13	花镇东，贾薇，刘翠梅，等. 新精神活性物质分析手册：质谱分册[M].2版.北京：中国人民公安大学出版社，2019：289-337.
	HUA Z D， JIA W， LIU C M， et al. Hand book for the analysis of new psychoactive substance： Mass spectrometry parts[M]. 2nd ed. Beijing： Chinese Peo-ple’s Public Security University Press，2019：289-337.

质荷比（m/z）	相对丰度/%
220	1.80
137	7.49
126	100.00
109	10.04
96	5.94
84	5.66
55	6.25

质荷比（m/z）	相对丰度/%
220	1.80
137	7.49
126	100.00
109	10.04
96	5.94
84	5.66
55	6.25

位置	碳谱		氢谱
位置	δ（¹³C）/×10^-6	峰型	δ（¹H）/×10^-6	质子数	峰型
1	14.06	单峰	0.78	3	三重峰
2	18.76	单峰	1.24~1.35	2	多重峰
3	32.89	单峰	2.03	2	多重峰
4	66.20	单峰	5.72	1	多重峰
5	52.60	单峰	3.36~3.81	2	双-多重峰
6	23.80	单峰	2.11~2.22	2	双-多重峰
7	23.65	单峰	2.11~2.22	2	双-多重峰
8	52.40	单峰	3.36~3.81	2	双-多重峰
9	132.84（J=7.0 Hz）	双峰	7.93	1	双重峰
10	14.56（J=3.2 Hz）	双峰	2.27	3	双重峰
11	116.01（J=17.9 Hz）	双峰	7.05	1	多重峰
12	129.38（J=9.7 Hz）	双峰	7.96	1	多重峰
13	126.48（J=17.9 Hz）	双峰	-	-	-
14	165.40（J=257.1 Hz）	双峰	-	-	-
15	131.40（J=2.9 Hz）	双峰	-	-	-
16	195.25	单峰	-	-	-
HCl	-		11.49	1	宽单峰

位置	碳谱		氢谱
位置	δ（¹³C）/×10^-6	峰型	δ（¹H）/×10^-6	质子数	峰型
1	14.06	单峰	0.78	3	三重峰
2	18.76	单峰	1.24~1.35	2	多重峰
3	32.89	单峰	2.03	2	多重峰
4	66.20	单峰	5.72	1	多重峰
5	52.60	单峰	3.36~3.81	2	双-多重峰
6	23.80	单峰	2.11~2.22	2	双-多重峰
7	23.65	单峰	2.11~2.22	2	双-多重峰
8	52.40	单峰	3.36~3.81	2	双-多重峰
9	132.84（J=7.0 Hz）	双峰	7.93	1	双重峰
10	14.56（J=3.2 Hz）	双峰	2.27	3	双重峰
11	116.01（J=17.9 Hz）	双峰	7.05	1	多重峰
12	129.38（J=9.7 Hz）	双峰	7.96	1	多重峰
13	126.48（J=17.9 Hz）	双峰	-	-	-
14	165.40（J=257.1 Hz）	双峰	-	-	-
15	131.40（J=2.9 Hz）	双峰	-	-	-
16	195.25	单峰	-	-	-
HCl	-		11.49	1	宽单峰

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