液相層析串聯質譜儀於毛髮檢驗之多元開發與應用

Development and Multi-application of Hair Testing by Liquid Chromatography Tandem Mass Spectrometer

陳秀娟(Hsiu-Chuan Chen)

指導教授 ： 張耀仁

中山醫學大學/醫學院/醫學研究所/博士(2022年)

https://doi.org/10.6834/csmu202200192

摘要

毛髮檢體體積小，具有採樣容易、不易摻假、不需冷凍冷藏，在運送與保存十分方便，更可透過分段分析回溯數月甚至數年的用藥史。本論文以發展前處理方法，以LC-MS/MS分析為檢驗技術平台，建立高效率高靈敏的毛髮檢驗方法。由於要溫和有效的取出毛髮中毒藥物，需要長時間的浸泡，採用微波輔助萃取，將浸泡取出時間縮短為數分鐘，大幅節省檢體製備時間。因此，第一部分研究是將微波輔助萃取應用於毛髮中檳榔、香菸生物鹼及代謝物的偵測，並評估有嚼食檳榔及吸菸習慣者之毛髮檢體，期望能用於戒治計畫與器官移植之評估。第二部分研究則發展單髮微區毛髮檢驗，將常見濫用藥物毛髮檢驗，包含安非他命、甲基安非他命、MDMA、MDA、K他命、去甲基K他命、嗎啡及6-乙醯嗎啡等，搭配快速的微波輔助萃取前處理方法與化學衍生化方法，將原本需要20毫克毛髮量與以月為單位的分段分析，縮小為單髮與以日為單位，並解決檢體數大幅增加與檢體量大幅減少之困難。第三部分研究，則針對新精神影響物質 (新興毒品) 之盛行，發展21種合成卡西酮毒品 (Synthetic cathinones) 及29種合成大麻毒品 (Synthetic cannabinoids) 之多重新興毒品檢驗方法，並分析高危險族群之毛髮，來了解國內相關濫用藥物趨勢。

關鍵字

毛髮檢驗 ； 液相層析串聯質譜 ； 檳榔鹼 ； 菸鹼 ； 濫用藥物

並列摘要

Hair testing provides several advantages, such as the simplicity of sample collection, storage and transportation, and hair is not easily adulterated. In addition to the above-mentioned advantages, hair samples could be cut into segments for analysis to provide a drug use history. The main purpose of this thesis is to develop high throughput and sensitivity LC-MS/MS methods of hair testing. We developed a fast extraction method based on micro-wave-assisted extraction to reducing the incubation time for analysts from hair. Firstly, an isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to detect the four biomarkers of betel nuts and cigarettes, including areca alkaloids (arecoline), tobacco alkaloids (nicotine), and their metabolites (arecaidine and cotinine). Secondly, a high sensitive and high throughput method for detecting most abused classic drugs and their metabolites, including methamphetamine (MA), amphetamine (AMP), methylenedioxy-methamphetamine (MDMA), methylenedioxyamphetamine (MDA), ketamine (K), norketamine (NK), 6-acetylmorphine (6-AM), and morphine (MOR) in a micro-segment of a single hair. Microwave-assisted extraction and derivatization were used to increase the throughput and sensitivity of selected drugs. Due to new psychoactive substances (NPS) of synthetic cathinones and synthetic cannabinoids abuse cause serious problems in the worldwide. The aim of third topic was the development of method to quantify 21 synthetic cathinones and 29 synthetic cannabinoids in hair, to assess the poly-consumption. The methods were applied to analyst real hair samples from high risk users of psychoactive drugs.

並列關鍵字

Hair testing ； Liquid chromatography–tandem mass spectrometry ； Areca nut alkaloids ； Tobacco alkaloids ； Drugs of abuse

參考文獻

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