目的: 探讨依托咪酯及其类似物在质谱下的裂解规律,为该类物质的鉴定及结构分析提供参考。方法: 基于气相色谱-四极杆飞行时间质谱（GC-Q TOF MS）联用技术和液相色谱-静电场轨道阱质谱（LC-Q Orbitrap MS）技术在EI和ESI正电离模式下对依托咪酯、美托咪酯、丙帕酯和异丙帕酯进行质谱分析,推测该类物质的EI-MS以及ESI-MS/MS裂解规律。结果: 依托咪酯及其类似物具有相似的裂解途径,在EI-MS模式下断裂过程主要集中在碳氮键的断裂,形成特定的离子碎片（m/z 105和m/z 77）。在ESI-MS/MS正离子模式下断裂过程主要集中在碳氮键的断裂,形成以苯乙烯为中性丢失的特征碎片离子,接着依次丢失中性碎片R1及H2O,形成特定的离子碎片（m/z 113和m/z 95）。此外,在ESI-MS/MS正离子模式中丢失的中性碎片R1可以较直观地反映母核上的取代基,从而进一步确定依托咪酯及其类似物结构。结论: 依托咪酯及其类似物质谱裂解规律有助于对该类物质的结构进行解析与推断,为法庭科学实验室该类物质的鉴定及结构分析提供参考。
Objective: To explore the fragmentation patterns of etomidate analogues by mass spectrometry to provide reference for the identification and structural analysis of these substances. Methods: Etomidate, metomidate, propaxate and isopropaxate were analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q TOF MS) and liquid chromatography high-resolution mass spectrometry (LC-Q Orbitrap MS) under EI and ESI positive ionization modes. And the EI-MS and ESI-MS/MS fragmentation patterns of etomidate analogues were deduced. Results: Etomidate and its analogues had similar fragmentation pathways. In EI-MS mode, the fragmentation pathway was mainly focused on the breaking of carbon-nitrogen bonds, and the specific fragment ions (m/z 105 and m/z 77) were formed. In ESI-MS/MS positive ion mode, the fragmentation pathway was mainly focused on the fracture of carbon-nitrogen bond, resulting in the formation of the characteristic fragment ion with styrene as neutral loss, Subsequently, the neutral fragments R1 and H2O were lost in turn, and the specific fragment ions (m/z 113 and m/z 95) was formed. Moreover, the neutral loss of R1 in ESI-MS/MS positive ion mode could more intuitively indicate the substituents on the parent nucleus and further determine the structure of etomidate and its analogues. Conclusion: The fragmentation patterns of etomidate and its analogues are helpful to analyze and infer the structure of these substances, and provide reference for the identification and structural analysis of these substances in forensic laboratory.
[1] DOENICKE A, KUGLER J, PENZEL G, et al.Cerebral function under etomidate, a new non-barbiturate i.v. hypnotic (author’s transl)[J]. Anaesthesist, 1973, 22(8): 357
[2] 王太云,刘宜平,李恩有. 依托咪酯常见不良反应及预防新策略研究进展[J]. 中国医药,2021,16(9): 1411
WANG TY, LIU YP, LI EY.Research progress on common adverse reactions of etomidate and new prevention strategies[J]. China Med, 2021, 16(9): 1411
[3] YU KJ, SOO YY, SEON YK, et al.Simultaneous determination of etomidate and its major metabolite, etomidate acid, in urine using dilute and shoot liquid chromatography-tandem mass spectrometry[J]. Molecules, 2019, 24(24): 4459
[4] 二〇二一年中国毒情形势报告[N]. 中国禁毒报,2022-06-28(003)
China Drug Situation Report2021[N]. China Narcotics Control News, 2022-06-28(003)
[5] 吴永富,王燕军,代勇,等.毛发、尿液中依托咪酯及代谢物HPLC-MS/MS 检测[J/OL]. 刑事技术,2024[2024-11-18]. https://doi.org/10.16467/j.1008-3650.2024.0011
WU YF, WANG YJ, DAI Y, et al.Determination of etomidate and its metabolite in hair and urine by HPLC-MS/MS[J/OL]. Forensic Sci Technol, 2024[2024-11-18]. https://doi.org/10.16467/j.1008-3650.2024.0011
[6] 黄楚舒,胡庆坤,高伟杰,等.新型毒品替代物丙帕酯和异丙帕酯的结构表征与分析[J/OL]. 刑事技术,2024[2024-11-18]. https://doi.org/10.16467/j.1008-3650.2024.0080
HUANG CS, HU QK, GAO WJ, et al.Structural characterization and comparative analysis of new drug substitutes propoxate and isopropoxate[J/OL]. Forensic Sci Technol, 2024[2024-11-18]. https://doi.org/10.16467/j.1008-3650.2024.0080
[7] YUM H, JEONG S, JANG M, et al.Fast and reliable analysis of veterinary metomidate and etomidate in human blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a postmortem case[J]. J Forensic Sci, 2021, 66(6): 2532
[8] 范一雷,陈显鑫,吴昊,等. 合成大麻素类新精神活性物质EI质谱特征研究[J]. 药物分析杂志,2024,44(9): 1463
FAN YL, CHEN XX, WU H, et al.Fragmentation patterns of synthetic cannabinoids based on electron impact ionization mass spectrometry[J]. Chin J Pharm Anal, 2024, 44(9): 1463
[9] 马俊,闫昕,张腾,等. 高效液相色谱-串联质谱法测定电子烟油中的替来他明和依托咪酯[J]. 中国司法鉴定,2024(3): 55
MA J, YAN X, ZHANG T, et al.Determination of tiletamine and etomidate in e-cigarette oil by HPLC-MS/MS[J]. Chin J Forensic Sci, 2024(3): 55
[10] SONG CH, JIA W, LIU CM, et al.New trends of new psychoactive substances(NPS)-infused chocolate: identification and quantification of trace level of NPS in complex matrix by GC-MS and NMR[J]. Talanta, 2023, 255: 124257
[11] 刘雪燕,贾薇,刘翠梅,等. 核磁共振波谱用于可疑样品中依托咪酯的定量研究[J/OL].分析试验室,2024[2024-11-18]. https://link.cnki.net/urlid/11.2017.TF.20240321.1105.013
LIU XY, JIA W, LIU CM, et al. 1H-qNMR for the quantification of etomidate in suspicious samples[J/OL]. Chin J Anal Lab, 2024[2024-11-18]. https://link.cnki.net/urlid/11.2017.TF.20240321.1105.013
[12] 范一雷,陈显鑫,张宏建,等. 质谱识别新型合成苯环己哌啶类物质氟胺酮异构体[J]. 分析试验室,2023,42(3): 338
FAN YL, CHEN XX, ZHANG HJ, et al.Differentiation of novel synthetic phenylcyclohexyl piperidines fluamine isomers by mass spectrometry[J]. Chin J Anal Lab, 2023, 42(3): 338
[13] NAN Q, HEJIAN W, PING X, et al.Investigation of fragmentation pathways of fentanyl analogues and novel synthetic opioids by electron ionization high-resolution mass spectrometry and electrospray ionization high-resolution tandem mass spectrometry[J]. J Am Soc Mass Spectrom, 2020, 31(2): 277
[14] 刘翠梅,花镇东,黄钰,等. 氯胺酮结构类似物的质谱特征研究[J]. 质谱学报,2023,44(4): 508
LIU CM, HUA ZD, HUANG Y, et al.Mass fragmentation characteristic of ketamine analogues[J]. J Chin Mass Spectrom Soc, 2023, 44(4): 508
[15] 范一雷,陈显鑫,薛锦锋,等. 新型靛红腙类合成大麻素质谱裂解规律研究[J]. 分析试验室,2024,43(1): 57
FAN YL, CHEN XX, XUE JF, et al.Investigation of mass spectrometry-based fragmentation patterns of new “OXIZZID” synthetic cannabinoids[J]. Chin J Anal Lab, 2024, 43(1): 57
[16] 赵永信,陈关喜,柯颖芬,等. 气相色谱-质谱法研究3-氧代戊酸酯烯醇-酮互变体质谱断裂途径[J]. 分析化学,2008,36(10): 1375
ZHAO YX, CHEN GX, KE YF, et al.Analysis of mass spectral fragmentation of enol-keto tautomers of some 3-oxo pentanoate esters by gas chromatography-mass spectrometry[J]. Chin J Anal Chem, 2008, 36(10): 1375
