基於兒茶酚衍生物相互作用的藥物和甜味劑的分析方法

Analytical Methods for Drugs and Sweeteners Based on Their Interaction with Catechol and Its Derivatives

黎武簪纓(Le Vu Tram Anh)

指導教授 ： 鄭淑華

國立暨南國際大學/科技學院/應用化學學系/博士(2019年)

https://doi.org/10.6837/ncnu201900082

摘要

本論文涵蓋三個主題，主要是闡述兒茶酚及其衍生物和待測分析物(藥物與甜味劑)之間的相互作用，並透過電化學和比色法開發出多種分析方法的應用。
在第一部分，主要是將兒茶酚和多壁奈米碳管(multi-walled carbon nanotubes, MWCNT)修飾於網版印刷碳電極(screen-printed carbon electrode, SPCE)上，製作出SPCE/MWCNT-COOH/CA-pCA電極，並發現此複合物修飾電極能夠輔助乙醯胺酚(acetaminophen, ACAP)的氧化還原反應。本研究以SPCE/MWCNT-COOH/CA-pCA修飾電極來進行ACAP的電化學分析，其線性範圍為0.5 μM至100 μM，而檢測限(LOD, S/N = 3)為15 nM。本研究所開發出的ACAP分析方法具有檢驗快速且符合經濟效益，並發現此電極具有良好的穩定性和再利用性，是本研究的重大突破。
在第二部分的章節中，我們提出阿斯巴甜(aspartame, ASP)的分析方法，是將已預氧化處理的網版印刷碳電極(SPCE*)放入含咖啡酸(caffeic acid, CAF)和ASP混合溶液中掃描，讓電極表面上產生共聚合化合物來偵測ASP，而在CV圖中觀察到兩對不同的氧化還原對，分別來自聚咖啡酸(poly(CAF))和CAF-ASP的共聚物(poly(CAF-ASP))。本研究透過poly(CAF-ASP)聚合物的電流變化來測定ASP，並以微分脈衝伏安法(differential pulse voltammetry, DPV)進行ASP的定量，發現在0.05 μM至10 μM ASP濃度範圍內具有線性關係，且偵測極限(LOD, S/N = 3)為0.0076 μM，並將此分析方法應用於碳酸飲料中甜味劑的測定。根據研究結果發現碳酸飲料中的食品添加劑並不會干擾ASP的偵測，以標準添加法來測定可口可樂和Coke Zero這兩種碳酸飲料中的ASP含量，其回收率分別在103.0 ~ 106.7％和97.3 ~ 106.4％之間，並採用高效能液相層析光譜法(high performance liquid chromatography, HPLC)進行同步驗證，並獲得一致性的分析結果，證實本研究開發的ASP分析方法具有良好的準確性，能應用於真實樣品的測定。
本論文的最後的章節，主要是論述奈米金粒子(gold nanoparticles, AuNPs)會受到溶液中共同存在多巴胺(dopamine, DA)和磺胺(sulfanilamide, SAA)交互影響，而產生AuNPs的聚集和分散性，因而開發出比色法來定量SAA。原本水溶液中的AuNPs是由檸檬酸根離子作為保護劑，而當溶液中出現DA時，DA會取代檸檬酸根離子的位置而形成DA-AuNPs，因而影響AuNPs的分散性並導致AuNPs溶液的顏色改變；但當溶液中添加SAA時會延遲AuNPs的聚集，因此可應用此原理開發SAA的檢測。本研究並以TEM圖去驗證AuNPs的狀態變化。在最佳化條件下，在0.5至80.0 μM SAA具有良好線性範圍，其偵測極限為0.3 μM。由研究結果發現抗壞血酸、甘胺酸、水楊酸、L-絲胺酸都不會干擾SAA測定。本研究使用標準添加法去檢測牛奶和豬肉樣品中的SAA含量，並獲得良好的回收率。

關鍵字

網版印刷碳電極 ； 兒茶酚 ； 乙醯胺酚 ； 多壁奈米碳管 ； 電聚合 ； 咖啡酸 ； 阿斯巴甜 ； 共聚物 ； 奈米金粒子 ； 磺胺 ； 多巴胺 ； 比色法

並列摘要

This thesis includes three topics that investigate the vital role of catechol and its derivatives in their interaction with some drugs and sweeteners using electrochemical and colorimetric methods. These strategies are utilized for versatile analytical applications.
In the first part, the combination of catechol and multi-walled carbon nanotubes (MWCNTs) is used as modifiers on screen-printed carbon electrode (SPCE) to promote the redox reaction of acetaminophen (ACAP). At SPCE/MWCNT-COOH/CA-pCA electrode, a linear range was observed for ACAP concentration from 0.5 µM to 100 µM and the detection limit (LOD, S/N = 3) was 0.2 µM. The electrode stability and reuse ability are the highlight points of this method when a quick and economical ACAP analysis method is required.
In later section, we propose a method for determining aspartame (ASP) when it was co-electropolymerized on preanodized SPCE* in the presence of caffeic acid. Two distinct redox peaks were observed at SPCE* due to the formation of a homopolymer poly(CAF) and a copolymer poly(CAF-ASP). Current responses from poly(CAF-ASP) were employed for ASP determination, and a linear dynamic range from 0.05 µM to 10 µM was obtained using differential pulse voltammetry (DPV). The limit of detection (LOD, S/N = 3) was 0.0076 µM. Common additives in soft drinks do not interfere with the ASP analysis. The proposed assay was applied for the determination of ASP in two soft drinks using the standard addition method, and recoveries in the range of 103.0–106.7% and 97.3–106.4% were obtained for Coca-Cola and Coke Zero, respectively. A reference high-performance liquid chromatography (HPLC) was applied to validate the proposed method, and good agreement was obtained.
Follow the above sections, a colorimetric method was developed based on gold nanoparticles (AuNPs), in which the aggregation and dispersion states are effected by the presence of dopamine (DA) and sulfanilamide (SAA) in the same solution. In the citrate ions surrounded gold nanoparticles solution, the addition of DA showed apparent color change, implying the change of AuNPs dispersion state to aggregation state due to the formation of DA-AuNPs. The adding of SAA in the same solution postponed the aggregation of AuNPs, which was utilized for SAA detection. The state changing of AuNPs were confirmed by TEM images. Under optimized conditions, a good linear range of SAA concentrations from 0.5 µM to 80.0 µM was obtained and the limit of detection (LOD, S/N = 3) is 0.3 µM. Interference studies indicate that ascorbic acid, salicylic acid, sulfanilic aicd, amino acids and other sulfa drugs do not interfere with SAA assay. The proposed method was applied to detect SAA in milk and pork samples using the standard addition method and satisfactory spiked recoveries are obtained.

並列關鍵字

Screen-printed carbon electrode ； catechol ； acetaminophen ； multi-walled carbon nanotubes ； electropolymerization ； caffeic acid ； aspartame ； co-polymer ； gold nanoparticles ； sulfanilamide ； dopamine ； colorimetry

參考文獻

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