新一代毛髮檢驗之液相層析串聯質譜方法開發與應用拓展

毛髮屬長效性的生物檢體，相較血液與尿液，具有許多優點，最主要可提供長達數週、數月甚至數年的檢測時窗。本研究將利用毛髮檢體，發展高效率的檢體前處理與高靈敏的液相層析串聯質譜 (LC–MS/MS) 分析方法，以提升毛髮檢驗的通量與分析靈敏度。首先，發展常見濫用藥物的高通量毛髮檢驗方法，藉由微波輔助藥物從毛髮取出，可有效改善縮短藥物從毛髮中取出的時間。再以不經萃取的前處理流程，直接進行 LC–MS/MS 的分析，更顯著提升毛髮檢驗之通量。其次，開發高靈敏的毛髮中大麻酸分析方法，利用簡單且快速的化學衍生方式 (Dansylation)，增加化合物於電噴灑游離化 (ESI) 時的效果，以提升在 LC–MS/MS 分析的靈敏度。再者，發展毛髮檢體中的塑化劑 (DEHP) 代謝物的 LC–MS/MS 分析方法，並探討最佳的毛髮浸泡溶液。成功測得毛髮中 DEHP 代謝物後，進一步以鹼性的浸泡溶液改善毛髮中 DEHP 代謝物的取出，再發展為更快速的自動化連線固相萃取 (On-line SPE) 方法直接結合 LC–MS /MS 分析，不僅更省時也可增加分析通量。此方法應用於毛髮的分段分析研究，可呈現人體不同時期的 DEHP 暴露趨勢。最後，將毛髮檢體應用來分析經人體代謝後會產生出安非他命的減肥藥物 clobenzorex，藉由毛髮能保存較多原態藥物的特色，以提供 clobenzorex 於常規尿液檢驗時可能誤判的佐證。

關鍵字

毛髮檢驗；液相層析串聯質譜；濫用藥物；塑化劑；大麻；前驅藥物

並列摘要

Compared to blood and urine, hair is unique in that it could determine the time period of chemical exposure after several months to years. The main purpose of this study is to develop high throughput and sensitivity analysis method of hair testing. Firstly, we developed a fast microwave-assisted extraction method for reducing the incubation time of abused drug release from human hair. In addition, extraction-free sample preparation and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis are evaluated for improving throughput of experiments. Secondly, a high sensitive method for detecting trace amount THC-COOH in hair by using strategy of simple and fast chemical derivatization with dansyl chloride coupled with LC–MS/MS. Thirdly, a stable isotope dilution liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed to detect the metabolites of human DEHP exposure in hair. We investigated the incubation conditions for improving the releae efficiency of metabolites from hair. Furthermore, an automated on line solid-phase extraction (On-line SPE) coupled with LC–MS/MS system was developed for reducing experiment time and increasing the high-throughput of analysis. In particular, the authentic hair specimens were determined and perfromed of segmental hair analysis for proving the practicability of assessing DEHP exposure in human hair. Consequently, an LC–MS/MS method was developed and utilized to authentic hair that could be successfully determined of parent compound of clobenzorex to discriminate the truly condition of clobenzorex used while not AMP.

並列關鍵字

Hair testing ； Liquid chromatography–tandem mass spectrometry ； Drug of abused ； Phthalate ； THC-COOH ； Clobenzorex

參考文獻

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2. Marigo M, Tagliaro F, Poiesi C, Lafisca S, Neri C. Determination of morphine in the hair of heroin addicts by high performance liquid chromatography with fluorimetric detection. J. Anal. Toxicol. 1986;10:158-161.

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新一代毛髮檢驗之液相層析串聯質譜方法開發與應用拓展

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