使用氣相層析質譜儀檢測尿液中苯胺類濫用藥物方法之開發研究

Novel Method for the Determination of Urinary Phenylamine Abused Drugs Using Gas Chromatography-Mass Spectrometry

黃明坤(Min-Kun Huang)

指導教授 ： 黃賢達

國立清華大學/理學院/化學系/博士(2006年)

https://doi.org/10.6843/NTHU.2006.00536

摘要

摘要

本論文中，共完成四篇有關在台灣及其他國家濫用之苯胺類濫用藥物檢驗方法之研究報告。利用固相微萃取（SPME）法及固相萃取（SPE）法，並使用Heptafluorobutyric anhydride/Heptafluorobutyric chloride (HFBA/HFBCl)或N-methyl-bis(trifluoroacetamide) (CF3CONCH3COCF3, MBTFA)做為衍生化劑，使其產生較易揮發、較具熱穩定性、及較大分子量之衍生物使其易於在氣相層析質譜儀（GC-MS）中進行分析檢測。

　 在第一篇研究報告中，我們使用頂空固相微萃取法來萃取尿液中之安非他命(Amphetamine, AMP)及甲基安非他命(Methamphetamine, MTH)，並同時使用HFBA/HFBCl做為衍生化劑，使萃取及化學衍生同時完成，讓待測物附著於SPME之纖維上，接著打入GC-MS中進行分析。依本方法所得到之安非他命及甲基安非他命濃度推算，可得到約10 %之回收率，這是一般使用SPME方法很難得到之結果。

在第二篇研究報告中, 我們使用高沸點之衍生化劑MBTFA來衍生愷他命(Ketamine, KT)、去甲基愷他命(Norketamine, NK)及去氫去甲基愷他命(Dehydronorketamine, DHNK)。本篇研究報告所開發之分析方法可成功的運用於尿液中KT、NK及DHNK之定量檢測。

由於近年來，多重濫用藥物之逐漸盛行，我們的第三篇研究報告係運用第二篇報告中之分析方法發展了可同時檢測MTH、 AMP、搖頭丸（包括MDMA、MDA及MDEA)、 KT, NK及 DHNK等八種藥物之方法，經方法評估之結果，八種藥物均可得到良好之回收率、再現性及檢測敏感度。

在第四篇研究報告中，我們發展了同時檢驗4-bromo-2,5-dimethoxyphenethylamine (2C-B)、4-chloro-2,5-dimethoxyphenethylamine (2C-C)及4-iodo-2,5-dimethoxyphenethylamine (2C-I)之分析方法，該等藥物之標準品在市面上無法購得，必須自行或委託其他單位合成。本分析方法與前面在第二、三篇研究報告之方法相似，使用SPE萃取，再以 MBTFA衍生，最後再注入GC-MS進行分析。同樣的，本分析方法亦得到良好之方法評估結果。

雖然我們已經完成了四篇研究報告，但相關之研究並未因此而結束，例如進行SPME萃取時，是否可以MBTFA取代HFBA/HBCl 或是SPME是否亦可應用於愷他命及2C-B、2C-C及2C-I等藥物之分析，仍有必要未來持續進行研究。

關鍵字

氣相層析質譜儀 ； 尿液 ； 安非他命類 ； 愷他命 ； 固相微萃取

並列摘要

Abstract

In this thesis, we have completed four articles focused on the detection of some abused phenalkylamines found in Taiwan and the other countries. Solid-phase microextraction (SPME) and solid-phase extraction (SPE) methods were applied to extract these drugs and some of their metabolites in urine, then these compounds were derivatized with Heptafluorobutyric anhydride/Heptafluorobutyric chloride (HFBA/HFBCl) or MBTFA to yield more volatile, more stable, higher molecular weight, and easily detectable targets for GC-MS using selected ion monitoring mode (SIM).
　In the first article, we extracted amphetamine (AMP) and methamphetamine (MTH) using headspace-SPME method, and finished the derivatization procedure on the SPME fiber at the same time. After gas chromatography-mass spectrometry (GC-MS) injection, we got about 10 % of recovery for both of AMP and MTH.
In the second article, we applied a high boiling point acylation reagent, N-methyl-bis(trifluoroacetamide) (CF3CONCH3COCF3, MBTFA), to derivatize and detect ketamine (KT), norketamine (NK), and dehydronorketamine (DHNK). This proposed process achieves high sensitivity to detect these three compounds. The analytical method was also applied to determine the concentration of KT, NK, and DHNK in some suspected urine specimens.
Because polydrug abuse were found in recent years, an analytical method for simultaneous determination of MTH, AMP, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), KT, NK, and DHNK in urine is described in the third article. The sample preparation and detection method is similar as those in the second article. Excellent linear regression, overall recoveries, and detection limit is obtained for all of these eight compounds.
In the last article, an analytical method for simultaneous determination of some new abused drugs, 4-bromo-2,5-dimethoxyphenethylamine (2C-B), 4-chloro-2,5-dimethoxyphenethylamine (2C-C), and 4-iodo-2,5-dimethoxyphenethylamine (2C-I), is developed. Because the lack of these halogenated compound in the commercial market, the standards should be synthesized in the laboratory. The analysis of these drugs is based on SPE and chemical derivatization (ChD) using MBTFA. These derivatized compounds are then separated and detected using GC-MS. Like the other three developed methods, excellent method validation results were achieved.
Although we have completed four studies, but more advanced studies in this related field may be proceeded continuously, such as using MBTFA to replace HFBA/HBCl as ChD reagent in the one step SPME procedure, extracting and derivatizing KT in the SPME method, or detectinging AMP, KT and 2C-Bs simultaneously in the SPE process.

並列關鍵字

GC-MS ； Urine ； Amphetamines ； Ketamine ； SPME

參考文獻

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