哌類成癮性藥物的分離與分析

Abstract

哌泛指具有兩個相對的含氮六員環有機化合物。此類化合物除應用於工業用途上，部份具有藥理作用，如止痛、麻醉、抗抑鬱等。少數哌結構的化合物具有興奮和幻覺效果。目前哌類成癮性藥物在國內雖然尚未列屬管制藥物，但在被濫用之前，建立確實的分離與分析方法則極為重要。本研究使用的七種哌類成癮性藥物，包括 1-(3-chlorophenyl)piperazine 、1-(5-trifluromethylphenyl)piperazine 1-benzylpiperazine、4-bromo-2,5-dimethoxy-1-benzylpiperazine、1-(4-methoxyphenyl)piperazine 、1-benzyl-4-methylpiperazine 以及3,4-methylenedioxybenzyl)piperazine；分別使用氣相層析質譜法(GC/MS)、液相層析/電噴灑-四極柱式飛行時間型質譜法(LC/ESI-Q-TOFMS) 以及毛細管電動層析 (Micellar Electrokinetic Chromatography, MEKC) 進行分析。 使用 DB-5MS 毛細管柱作為 GC/MS 的分離管柱，在 15 分鐘內可完全將之分離，惟在 EI (electron impact)的模式之下，較難觀測到母離子峰的存在。選用 SIM (selected ion monitoring) 模式，各分析的偵測極限為~ 100 ppb。 相較於此，LC/ESI-Q-TOFMS 則較易用來觀測母離子峰；使用 C18 管柱，其動相的梯度分別為 10% MeOH -15% MeOH- 35% MeOH-40% MeOH (0-15-20-30 分鐘)，35 分鐘內可完全分離。在全掃描模式下 (full scan)，各分析的偵測極限為~ 1 ppm。因實驗所得到的母離子峰分子量與理論值有些微差異，因此本實驗利用自撰的程式對質譜作校正，使其可以有效提高精確度以及靈敏度。 毛細管微胞電動層析，將 50 mM 的 NaH2PO4、75 mM 的陰離子型界面活性劑 SDS 配製在 H2O:MeOH:ACN (v/v/v, 65:20:15) 的混合溶液中；作為背景溶液，20 分鐘左右即可完全分離，在此條件下偵測極限為~ 5 ppm。若配合線上濃縮堆積技術則可改良偵測極限至~ 5 ppb。The skeletal structure of piperazine is six-membered ring containing two nitrogen atoms. The piperazine analog compounds have pharmacological properties, such as anodynes, narcotics. Some compounds with piperazine structure have psychedelic effect. Piperazine compounds are psychedelic drugs. 1-benzylpiperazine (BZP) is regulated as illegal drugs in USA, Australia, Japan, and some European countries. Although the applications of those drugs haven’t been regulated in Taiwan, development of reliable and quick analytical methods is critical to drug abuse in the future. This thesis aims at the study of separation and characterization of piperazine abuse drugs. BZP and other six potential designer drugs of abuse were studied, including 1-(4-methoxyphenyl)piperazine, 1-benzyl-4-methylpiperazine, 1-(3,4-methylenedioxybenzyl)piperazine, 4-bromo-2,5-dimethoxy-1-benzylpiperazine, 1-(5-trifluromethylphenyl)piperazine and 1-(3-chlorophenyl)piperazine. Those compounds were separated and characterized with GC-MS, LC/ESI-Q-TOFMS and sweeping-MEKC methods. Analysis of GC/MS with DB-5MS column gave reliable analytical results within 15 minutes. The parent peaks were not observed in the electron impact mode. On the other hand, the parent peaks were observed in the LC/ESI-Q-TOFMS. By using C18 column with gradient mobile phase of 10% MeOH-15% MeOH-35% MeOH-40% MeOH (0-15-20-30 minutes), all piperazine compounds were separated completely in 35 minutes. In MEKC, mixture of 50 mM NaH2PO4, 75 mM SDS and H2O:MeOH:ACN(v/v/v, 65:20:15) buffer solution enabled the separation of the seven piperazine compounds in 30 minutes. The limits of detection (LOD) can be enhanced by coupling sweeping-MEKC. An essays program was developed to align mass spectra. It can improve the analytical precision and sensitivity. In addition, the fragmentation of piperazine compounds was characterized to assist the identification of abusing drugs.