第一部份 : 卡普洛芬於醇類溶媒之光解反應 第二部份 : 以高壓液
相層析法定量甲醇溶液中之那普洛辛及其方法驗證
I. Photolytic Studies of Carprofen in Alcoholic Solvents II.
Quantitation of Naproxen in Methanol by HPLC and Method Validation
中文摘要
本研究分為兩部份進行一系列光分解實驗。先將卡普洛芬(CPF)及那普洛辛(NAP)
分別置於醇類溶媒中如甲醇或乙醇，以Hanovia 200 W 高壓汞燈照射數小時下，
進行光解反應。
第一部份以管柱層析法將卡普洛芬光解產物分離，共得到三種主要的光解產物，
分別命名為 CPF 10、CPF 28 及 CPF 48。藉由質譜儀、紅外線光譜儀、核磁共振 氫譜及碳譜判斷：CPF 10 為 2-(2-carbazolyl) propionic acid；CPF 28 為
2-(2-carbazolyl) propionic acid, methyl ester；而 CPF 48 為 2-(6-chloro-2-carbazolyl) propionic acid, methyl ester。在乙醇溶液中則發現有相當於甲醇溶媒滯留時間的 CP 11、CP 28 及 CP 56 光解產物生成。CP 56 為乙基酯，為酯化反應之衍生物。
以上是以高效液相層析法(HPLC)於醇類溶液中監測卡普洛芬進行光解反應並以 各類光譜法決定CPF 10、CPF 28 及 CPF 48 產物構造的方法。
第二部份乃發展一個快速、敏感度高及準確的安定性指標的高壓液相層析法來定 量那普洛辛。對那普洛辛的分析方法是用Inertsil ODS-3V 管柱，移動相則採乙 腈:甲醇:水=40:20:40 (v/v/v) ，UV 偵測器則設定為 230 nm。就已發展出的分析 方法，其相關統計及確效包含有高壓液相層析系統規範、波峰純度完整以及光解
產物和原料藥之間的解析度，及日內、日間差異分別在4.56%和 3.82%以內。靈
敏度可偵測到極低的濃度，偵測極限(Limit of Detection；LOD)可測得之濃度為 64 ng/mL，而定量極限(Limit of Quantitation；LOQ)可測得之濃度為 0.29μg/mL。
由此可知，就建立的分析方法表現出良好的選擇性和特異性，適合用來作為那普 洛辛的光安定性的分析。
英文摘要
This thesis is divided into two parts. Carprofen or naproxen was placed in a polar solvent, methanol or ethanol separately, then it was exposed to a Hanovia 200 W high pressure mercury lamp.
Firstly, a series of photolytic study of Carprofen(CPF) was undertaken.The
photodegradants were separated and quantified by a HPLC method. Three photolytic products, CPF 10, CPF 28 and CPF 48, were isolated by the column chromatography.
By way of analyzing MS, NMR and IR spectra, their structures were characterized.
Their structures were identified as CPF 10, 2-(2-carbazolyl) propionic acid；CPF 28, 2-(2-carbazolyl) propionic acid, methyl ester；and CPF 48, 2-(6-chloro-2- carbazolyl) propionic acid, methyl ester. Similar photolytic products including CP 11, CP 28, and CP 56 were found in ethanol. CP 56, an ethyl ester of CPF 48 was found as a
derivative in ethanol. High-performance liquid chromatographic assay method was used for monitoring the degradation of CPF and its degradants-CPF 10, CPF 28, and CPF 48.
Secondly, we focused on the quantitation studies of the photochemical decomposition of Naproxen (NAP). A rapid, sensitive, and accurate stability-indicating high
performance liquid chromatographic assay method for determination of the
degradation of NAP was developed and validated under photoirradiated conditions.
The quantitation was monitored with an Inertsil ODS-3V column using a mobile phase of acetonitril : methanol : water = 40:20:40 (v/v/v). The UV detector was set at 230 nm. The related statistics of the developed methods including the system criteria, peak integrity, and resolution among the parent drug and its degradation products were calculated. The CV% of intraday and interday tests were lower than 4.56% and 3.82%, respectively. LOD (Limit of Detection) was 64 ng/mL, and LOQ (Limit of Quantitation) was 0.29μg/mL. Our established HPLC assay method shows good selectivity and specificity which is suitable for the stability measurement of NAP.
