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
Photolytic Studies of NSAIDs — Carprofen and Naproxen and Calcium Channel Blocker — Nicardipine by Liquid
Chromatography/Electrospray Ionization/Mass Spectrometry
中文摘要
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。
英文摘要
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 processes were thus understood by resolving and understanding the structures of the photodecomposition products.
The first part of this research involved the studies of NSAIDs-carprofen and naproxen.
The methanol solution 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 position in the
carbazole ring of the carprofen molecule was lost due to photochemical
dechlorination. It was also 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 that methanol played a vital role in the decomposition where the methyl ether derivatives of CAPI-3 and CAPI-6, were formed and the methyl ester
derivatives, CAPI-5 and CAPI-7 were yielded. The photodecomposition 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.
The second part of this research involved the photochemical decomposition of the calcium channel blocker nicardipine which was found to be an aromatization reaction of 1,4-dihydropyridine. The aromatization reaction was showed to be the first process to occur. The subsequent photodecomposition products were generated from this first process. The long chain ester was decomposed to form the demethylation and
demethoxylation products, whereas the ester group was hydrolyzed to form the corresponding carboxylic compounds. The photodecomposition of nicardipine containing a m-nitrobenzyl substituent was found to be dependent on the characteristics of the long chain ester functional groups in the molecule.
