近年來藥物市場的供應和使用量節節高升，且市售藥物中超過25%是以消旋或是結構異構物的型態來販售，因此環境藥物殘留的檢測越來越受矚目。雖然這些非類固醇鎮痛解熱劑(non-steroidal anti- inflammatory drugs，簡稱NSAIDs)的作用機制已經有20幾年的研究歷史了，但尚未明白殘留於環境中是否在未來對環境將造成什麼不可預期的影響。特別是具有掌性特性的藥物，因為不同掌性異構物對生物體的生物活性與毒性皆有所不同，因此研究環境中對掌藥物的含量與比例越來越受大家關注。本研究挑選兩個常用且含有掌性特性的非類固醇陣痛解熱劑－凱妥普洛芬和異布洛芬來當作目標待測物。分離管柱選擇α1-酸性醣蛋白掌性分離管柱(α1-acid glycoprotein chiral column，簡稱AGP掌性分離管柱)，搭配液相層析串聯質譜儀開發出可檢測環境不同水樣中掌性異構物比例的分析方法。在動相溶液中添加三級胺的電荷修飾劑－DMOA(N, N-dimethyloctylamine)可大幅改善掌性異構物之分離效果但會造成某程度上的基質干擾。比較三種不同遊離介面(ESI, APCI和APPI)的游離效果、基質干擾程度及偵測極限，來選擇最佳遊離介面。真實樣品則利用HLB固相萃取法萃取環境水樣中的待測物。本實驗的凱妥普洛芬之偵測極限(LOD)為100 ng/L，而添加之水樣掌性異構物回收率為50-100%，相對標準偏差皆在8以內，然而五個真實水樣中皆未偵測到凱妥普洛芬異構物的存在。雖然添加DMOA可以大幅改善待測物的滯留時間以及管柱掌性選擇性，但也會產生嚴重的基質干擾影響游離源的游離效果以及質譜偵測極限。 Currently, pharmaceuticals are supplied and used in abundance, their residues become major targets in environmental. More than 25% of pharma- ceuticals are market as either recemates or the mixture of diastereoisomers. Although non-steroidal anti-inflammatory drugs(NSAIDs) has been studied for over 20 years, the subsequent environmental occurrence, fate, and effects of these residues are not well understood, especially the effects of chiral residues in our environment. Chiral residues should be concerned because of their different biological and/or toxicological effects from one another. Two widely used NSAIDs, Ibuprofen and ketoprofen, were used as the model chiral compounds in our study. A method of chiral liquid chromatography-tandem mass spectro- metry(LC-MS/MS) was developed to determine the ibuprofen and ketoprofen enantiomers in various water samples. A chiral α1-acid glycoprotein (AGP) column was used to separate two enantiomers. The retention and the enantio- selectivity of the analytes can easily be regulated by addition of tertiary amine N, N-dimethyloctylamine (DMOA) to the mobile phase as a charge modifier. Moreover, various ionization techniques including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric photoionization (APPI) interfaced with chiral liquid chromatographic methods were evaluated with their ionization efficiencies, matrix effects and limitations. Water samples were extracted by HLB-solid-phase extraction. The limit of quantitation (LOQ) was 100 ng/L for ketoprofen enantiomers in 100 mL of water sample. The spiked recoveries of enantiomers ranged 50-100% while RSD was less than 8% (n=3). However, enantiomers were not detected in five selected water samples. Although DMOA can be added to improve the retention and enantioselectivity, of solute, it may bring seriously matrix effect to affect ionization efficience and detection limitation.
