以液相層析串聯質譜儀偵測毛髮中苯二氮平類藥物之研究與開發

Determination of Benzodiazepins in Hair using High Performance Liquid Chromatography - Tandem Mass Spectrometry

何芯汝(Shin-Ru Ho)

指導教授 ： 張耀仁

中山醫學大學/醫學院/醫學分子毒理學研究所/碩士(2010年)

摘要

苯二氮平類藥物 (Benzodiazepam，BZD) 一般多用於鎮靜、安眠之用途，但由於服用後會使人產生昏睡、失去反抗能力，甚至於喪失記憶，因此常成為不肖份子性侵害或約會強暴之工具。由於BZD 藥物使用劑量低，被下藥之受害者又常屬於一次施用，再加常需數週以上之心理調適期，因此取得被下藥之證據常屬不易。
毛髮檢體具有寬廣的檢驗時窗，能提供長時間性的藥物使用歷程，極適合用來取得被下藥之犯罪證據。本研究針對Diazepam、Nordiazepam、Oxazepam、Lorazepam、Nitrazepam、Temazepam、Flunitrazepam、Alprazolam、Triazolam等9種BZD 類藥物，以液相層析串聯質譜儀，發展毛髮檢測。研究首先建立多重反應監測模式(MRM) ，並發展高效率液相層析分離。為進一步提升分離效率與分析靈敏度，隨後搭配新型之Core-shell層析管柱，達到超高效液相層析 (UHPLC) 之效果，使波峰寬皆小於6秒鐘，總分離時間只需4.5分鐘。而最低偵測極限，除 7-aminoflunitrazepam為5 pg/mg hair外，其他藥物介於0.1 ~ 0.5 pg/mg 之間。研究最後進行UHPLC-MS/MS之評估，透過基質效應之評量、管柱之比較與真實毛髮檢體之分析，了解實務之需求與方法之適用性。

關鍵字

苯二氮平 ； 毛髮 ； 液相層析串聯質譜儀

並列摘要

Sedative agents are used to facilitate sexual assault due to their ability of rendering the victim passive, submissive and unable to resist. The benzodiazepine (BZD) acts on the central nervous system (CNS) to exert mainly sedation effects. To date, benzodiazepine is a kind of widely abused drug which usually be utilized for application of date-raping. Hair is a new alternative biological specimen which gets great attention in forensic science fields for its ability of trace back detection.
In this study, a liquid chromatography tandem mass spectrometry ( LC-MS/MS ) was used under multiple reaction monitoring (MRM) mode to determinate BZD and metabolites ( include diazepam, nordiazepam, oxazepam, lorazepam, nitrazepam, temazepam, alprazolam, triazolam, flunitrazepam and 7-aminoflunitrazepam ) in hair. Then, a new core-shell kinetex column was used to improve performance of HPLC into UHPLC results by harnessing the power of core-shell technology that can significantly improve the separation efficiency and sensitivity. These results indicate the developed method can provide the limit of detection (LOD) from 0.1 to 0.5 pg/mg for most BZDs, except for 7-aminoflunitrazepam.

並列關鍵字

Benzodiazepam ； Hair ； High Performance Liquid Chromatography - Tandem Mass Spectrometry

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