唾液中多重濫用藥物之質譜方法開發與探討

Saliva analysis for multiple drugs of abuse by mass spectrometry

蔡尚甫(Shang-Fu Tsai)

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(2009年)

https://doi.org/10.6834/CSMU.2009.00094

摘要

中文摘要
藥物濫用一直是全球性的重要問題，在國內的情況也日益嚴重。除了常見的安非他命、海洛因外，新興毒品包括K他命、搖頭丸、大麻等毒品的濫用也有逐漸增加的趨勢。唾液檢體，具有快速、方便、非侵入性的優點，因此唾液檢驗慢慢受到重視。本研究希望以GC/MS與LC/MS/MS同時分析不同種類的濫用藥物外，更將此分法應用到唾液檢體上，研究針對13種不同的濫用藥物及其代謝物進行廣泛性檢測，包含：甲基安非他命、安非他命、亞甲基雙氧甲基安非他命、亞甲基雙氧安非他命、Methylenedioxyethamphetamine、K他命、Norketamine、可待因、嗎啡、6-乙醯嗎啡、古柯鹼、Benzoylecgonine、大麻等。研究首先是發展GC/MS之唾液檢驗方法，唾液檢體經SPE萃取，隨後加入BSTFA進行矽化反應，最後以GC/MS分析。其次發展LC/MS/MS唾液分析方法，唾液檢體經萃取，隨後即進行分析。研究結果在 GC/MS 方面，發現以 BSTFA 衍生化試劑可同時分析13種不同的濫用藥物及其代謝物；另外 LC/MS/MS 方法則是較GC/MS得到更高的靈敏度與更快的前處理時間。未來不管是GC/MS或LC/MS/MS，如果能搭配更可靠的取樣方法，實際運用在臨檢的場合，不但可大幅增加濫用藥物檢測廣度，也提高了分析的效率。

關鍵字

濫用藥物 ； 唾液 ； 氣相層析質譜儀 ； 液相層析串聯質譜儀

並列摘要

Abstract
The increase in club drugs and poly-drug abuse requires the development of an easy and fast technique able to simultaneously detect a wide range of drugs using a low amount of specimen. Saliva can provide a non-invasive specimen for drug testing. In addition, the use of saliva to detect the presence of illicit drugs has become increasingly popular as a quick collection specimen to detect drug-use. In this study, we developed simultaneously quantitative method using GC/MS and LC/MS/MS for amphetamines (amphetamine; AP, methamphetamine; MA, methylenedioxyamphetamine; MDA, methylenedioxymethamphe tamine; MDMA, methylenedioxyethylamphetamine; MDEA), ketamine (ketamine; K, norketamine; NK), opiates (morphine; MOR, codeine; COD, 6-mono acetylmorphine; 6-AM), cocaine (cocaine; COC, benzoylecgonine; BZE) and cannabis (THCA) were test in saliva sample. Firstly, we studied the possibility of simultaneous testing of multi-drugs of abused testing in saliva samples using gas chromatography/mass spectrometry (GC/MS) after derivatized by HFBA. However, some popular drugs of abuse like cocaine and cannabis cannot be derivatized well by HFBA.
So we try to evaluate BSTFA derivatization for simultaneous drugs of abuse testing using GC/MS. The samples were extracted by solid-phase extraction (SPE), and then derivatized by BSTFA, and the derivatives were analyzed by GC/EI-MS with selected ion monitoring mode. All compounds were performed with a run time of 13 minutes. The limit of detection (LOD) obtained 10 ng/ml for AP, MA, NK, COD, MOR and 20 ng/ml for MDA, MDMA, MDEA, K, COC, BZE, 6-AM, THCA in saliva sample. Extraction recoveries were most >80%. Moreover, the saliva testing using LC/MS/MS was developed to detect the poly-drugs of abuse. The results indicate this method can provide high separation efficiency for those species and the LC/MS/MS can provide the greater limit of detect and quick sample preparation time. In conclusion, this study shows that integrating the characteristics of GC/EI-MS and LC/MS/MS were not only proved to be suitable for the confirmation testing to for determine illicit drug in saliva sample, but also will be used for a survey of drug use in scene.

並列關鍵字

Drugs of abuse ； Saliva ； GC/MS ； LC/MS/MS

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