新型苯二氮卓类策划药氯地西泮异构体质谱识别

Identification of new designer benzodiazepine chlorodiazepam isomers by mass spectrometry

采用液相色谱高分辨质谱(LC-Q-Orbitrap/MS)和气相色谱质谱(GC-MS)技术对新型苯二氮卓类策划药2’-氯地西泮和4’-氯地西泮的碎裂途径进行研究。在LC-Q-Orbitrap/MS中,由于七元杂环的结构相较于苯环稳定性更差,2’-氯地西泮和4’-氯地西泮主要是通过七元环裂解生成特征碎片离子m/z 154。在GC-MS中,由于2’-氯地西泮和4’-氯地西泮的苯环上电子云密度显著高于七元杂环,经电子轰击后,苯环更容易发生电离。因此,2’-氯地西泮和4’-氯地西泮经电子轰击失去一分子氯自由基,形成具有苯基正离子的特征碎片离子m/z 283。由于2’-氯地西泮失去一分子氯自由基形成2’-苯基正离子,能与N4位上孤对电子相互作用形成场效应,使得正离子不易进一步发生离域。因此,2’-氯地西泮生成的碎片离子m/z 283丰度高,而生成的碎片离子m/z 282丰度相对较低。4’-氯地西泮失去一分子氯自由基形成4’-苯基正离子,由于无法与N4位上孤对电子形成场效应,使得正离子能在苯环上离域,生成的碎片离子m/z283和m/z 282的丰度基本一致,并且相对2’-氯地西泮,生成碎片离子m/z 283的丰度低。因此,m/z 283与m/z 290的相对丰度可用于2’-氯地西泮和4’-氯地西泮的质谱识别,也可为类似混合物中新精神活性物质异构体的快速分离鉴定提供技术支持。

The fragmentation pathways of new designer benzodiazepine 2'-chlorodiazepam and 4'-chlorodiazepam were studied by liquid chromatography high-resolution mass spectrometry(LC-Q-Orbitrap/MS)and gas chromatography-mass spectrometry(GC-MS).In LC-Q-Orbitrap/MS,2'-chlorodiazepam and 4'-chlorodiazepam can produce easily the characteristic ion at m/z 154 by the cleavage of the seven membered ring due to the less stable structure of the seven membered ring compared to that of the benzene ring.In GC-MS,because the electron cloud density on the benzene ring of 2'-chlorodiazepam and 4'-chlorodiazepam was significantly higher than that of the seven membered ring,the benzene ring was prone to ionization after electron bombardment.Therefore,2'-chlorodiazepam and 4'-chlorodiazepam lost one molecule of chlorine radical by electron bombardment to form the characteristic fragment ion at m/z 283 with a phenyl positive ion.However,2'-chloroprazepam lost one molecule of chlorine radical to form 2'-phenyl positive ion,which could interact with lone pair of electrons at N4 position to form a field effect,making the positive ion difficult to undergo further delocalization.As a result,2'-chlordiazepoxide generated fragment ion at m/z 283 with high abundance while generating fragment ion at m/z 282 with relatively low abundance.In contrast,4'-chlordiazepoxide lost one molecule of chlorine radical to form the 4'-phenyl positive ion,which was unable to form a field effect with the lone pair of electrons at the N4 position,allowing the positive ion to delocalize on the benzene ring.For these reasons,the abundance of the fragment ions at m/z 283 and m/z 282 were basically the same,and lower than that of the fragment ion at m/z 283 of 2'-clodiazepam.Therefore,the relative abundance of m/z 283 and m/z 290 could be used for the identification of 2'-chlordiazepam and 4'-chlordiazepam,and can also provide technical support for the rapid separation and identification of new psychoactive substance isomers in similar mixtures.