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  • 學位論文

以丹磺醯衍生法搭配高性能液相層析串聯式質譜儀進行多重濫用藥物之同時分析

Simultaneous Determination of Multiple Drugs of Abuse by Dansylation and high-performance Liquid Chromatography Tandem Mass Spectrometry

指導教授 : 張耀仁

摘要


近年來毒品氾濫的情形日趨嚴重,除了常見的毒品外,更多種類的新興毒品也不斷的出現,不僅危害個人健康的,更對社會安定與國家發展造成極大之傷害。使用尿液檢體,以免疫方法進行初步檢驗,再針對初步檢驗超過閾值(cut-off)之檢體進行確認檢驗,為目前毒品的主要檢驗方式。然而尿液檢體必須儲存於低溫下,若檢出為陽性甚至可能需要保存長達一至二年,造成運送與保存之不便。如同新生兒遺傳疾病篩檢所用的乾血片一般,使用乾尿片具有容易運送與方便儲存之優點,然而目前尚無詳細之評估。 液相層析串聯質譜儀(LC-MS/MS)上雖有比氣相層析質譜儀(GC-MS)更高的靈敏度,然而預想到未來乾紙片可能遭遇之問題,因此本研究首先發展常見濫用藥物丹磺醯(Dansyl Chloride, DC)衍生化,針對DC可對藥物及其代謝物上之胺類(amines)或是酚類(phenol)官能基進行衍生,提升電灑法之游離化效率,並且其碎片離子更能大幅增強串聯質譜之靈敏度,來補強以乾紙片檢體檢驗的靈敏度不足之缺點。研究針對國內常見濫用藥物,包含安非他命類、嗎啡類、搖頭丸、K他命、大麻進行研究,選定原態藥物及代謝物共13種,進行DC衍生實驗之探討,並進一步行真實尿液及唾液檢體之比對,並初步針對乾紙片模擬檢體進行分析。實驗結果發現,經由良好的層析分離,我們可以將未衍生化合物與衍生化化合物適當分離,精確評估衍生化效率,獲得最佳衍生化效果。DC衍生對於酚類靈敏度有極顯著的提升效果,而微波衍生更可使反應時間降低至3分鐘。希望未來DC衍生能擴大至新興及更多濫用藥物,並且應用於真實檢體之乾紙片分析。

並列摘要


In recently years, the problem of the drugs of abuse become worse and worse, not only common drugs but also new popular drugs. The drugs of abuse problem result not just personal healthy, but also deplete national productivity. At present, urine is the most widespread sample for drug testing. Generally, immunoassay testing use in the first step, and then the positive samples should be examinated by confirmatory testing. But urine samples must store at low temperature for least 1-2 year, so that it is needed to improve for the cost of stored and transported. Therefore, the used dried filter paper, just like dried blood spots, is in our mind. Stored sample by dried filter paper can solve aforesaid question, but it is still unclear the method feasible or not. Although LC-MS/MS is much better sensitivity than GC-MS, it is maybe not enough for dried filter paper testing. Therefore, the use dansyl chloride derivative to enhance sensitivity of LC-MS/MS is developed in the study. Dansyl chloride derivative can react with phenol and primary, secondary amine. After derivative, the structure can enhance ionization at source of mass spectrometry, and the unique fragment ions can increase intensity in LC-MS/MS. the common abuse drugs are chose, including amphetamine, methamphetamine, MDA, MDMA, morphine, 6-acetyl morphine, codeine, cocaine, benzoylecgonine, ketamine, norketamine, tetrahydrocannabinol, tetrahydrocannabinol carboxylic acid, totally 13 compounds. Though the developed chromatography, the underivative and derivative compounds can be adequate separation. The efficiencis of derivative are estimated for optimum. The results are demonstrated that the chemical derivatization strategy with dansylation was improved not only the sensitivity but also the separation efficiency. Mostly, dansyl chloride derivative can be significant increase sensitivity of phenol compounds of LC-MS/MS, and microwave assisted derivatization reduce the reaction time to 3 min at 700 W. The dansyl chloride derivative can be expected usefully for dried filter paper with oral fluid and urine, and more drugs and further apply to the real samples.

並列關鍵字

drugs abuse dansyl chloride LC-MS/MS

參考文獻


[9] 柳家瑞,簡俊生,2007,〈質譜技術於藥物濫用防制之應用〉,
[1] 行政院衛生署等,2011,《100年反毒報告書》,臺北市 : 作者。
[6] 行政院衛生署,2003,《濫用藥物尿液檢驗作業準則》。
[7] 行政院衛生署,2011,《濫用藥物尿液檢驗作業準則》修改。
[26] Wu, Y. H., Lin, K. L., Chen, S. C., Chang, Y. Z. 2008. “Integration

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