以液相層析質譜儀分析 NSAID 藥物 - 卡普洛芬及那普洛辛之光解產物和 鈣離子阻斷劑 - 尼卡迪平之光解產物
本研究使用液相層析質譜儀來分析兩類藥物照光後之光解產物，藉由解開光 解產物構造以瞭解藥物照光後之可能反應過程。
第一部份以研究 NSAID 藥物包括卡普洛芬 (CAP) 及那普洛辛 (NAP) 。將卡 普洛芬溶於甲醇以高壓汞燈照射 ( 樣品 I) 或溶於 10 % 乙醇水溶液曝曬於太陽 光下 ( 樣品 II) ，則卡普洛芬 carbazole 環 C6 位置 氯之取代基照光後會進行 去氯基反應 (dechlorination) ，且為光解反應中反應速率最快且最先生成之產 物。 CAPI 經光解後生成 CAPI-1 至 CAPI-7 七種產物而 CAPII 生成 CAPII-1 至 CAPII-4 四種產物，觀察 CAPI 光解之特性乃溶媒 ( 甲醇 ) 效應係重要因素，如 CAPI-3 及 CAPI-6 乃甲基醚之衍生物；而 CAPI-5 及 CAPI-7 乃甲基酯之 產物。卡普洛芬溶液光解仍以去羧基反應 (decarboxylation) 及後續之氧化反應 (oxidation) 為主要反應途徑。而那普洛辛 (NAP) 之甲醇溶液經高壓汞燈照射 後可觀察到 NAP-1 至 NAP-3 三種光解產物。以上兩種 NSAID 藥物其光解反 應過程亦予詳細闡明。
第二部分以研究鈣離子阻斷劑藥物，尼卡迪平 (NIC) 進行光解生成 1,4- 二氫 吡啶芳香環化 (aromatization) 反應，它為反應速率最快且最先生成之反應，次 要光解產物均由 1,4- 二氫吡啶環化產物所生成，且光解反應作用在長鏈酯上，而產生去甲基及去甲氧基光解產物，酯鏈則因照光水解為羧酸產物，因此 我們得到在間位硝基苯基的尼卡迪平的光解需視其官能基之特性而產生。
Photolytic Studies of NSAIDs — Carprofen and Naproxen and Calcium Channel Blocker — Nicardipine by Liquid
Chromatography/Electrospray Ionization/Mass Spectrometry
The scope of this research focused on the LC-MS analysis and studies of the photochemical decomposition products of two classes of drugs; namely NSAIDs and calcium channel blockers. The photochemical proce sses were thus understood by resolving and understanding the structures of the photodecomposition produc ts.
The first part of this research involved the studies of NSAIDs-carprofen and naproxen. The methanol soluti on of carprofen (sample I) was subjected to high pressure Hg lamp irradiation and the 10% ethanol solution of carprofen (sample II) was subjected to natural sunlight. After the irradiation the chlorine at the C6 positi on in the carbazole ring of the carprofen molecule was lost due to photochemical dechlorination. It was als o found that the dechlorination product was the major product from such processes. Seven major products CAPI-1 to CAPI-7 were formed from the photochemical decomposition of carprofen and 4 major products CAPII-1 to CAPII-4 were generated from the sample decomposition process. The studies demonstrated tha t methanol played a vital role in the decomposition where the methyl ether derivatives of CAPI-3 and CAP I-6, were formed and the methyl ester derivatives, CAPI-5 and CAPI-7 were yielded. The photodecomposit ion of carprofen solution was found to proceed via decarboxylation and subsequent oxidation as the major routes. The methanol solution of naproxen after high pressure Hg lamp irradiation formed 3 major products NAP-1 to NAP-3. The photochemical reaction route of these two NSAIDs will be elucidated.
