以X光粉末繞射法評估非鏡像立體異構物d,l-CB-PAO
之立體化學純度
蔡長書
慈濟技術學院 放射技術系
摘 要
首先利用有機合成法製備CB-PAO非鏡像立體異構物，並以多次分步再結晶法有效分離d,l-型、 meso-型及非晶成份之立體異構物，另以熱分析法之微差掃描卡計 (DSC) 進行各成分熔點之測定。本研究嘗試以X光粉末繞射法 (XRPD) 建立一套可用來評估核醫藥物配位子d,l-CB-PAO非鏡像立體異構物之立體化學純度之可行性技術。根據XRPD特性型式，純化之d,l-型及meso-型的繞射峰特性指紋分別為2θ＝18.54°，d＝4.78 A及2θ＝10.87°，d＝8.13 A，非晶不純物成分為2θ＝18.92°，d＝4.67 A。以不同重量比例1：1，2：1及4：1之d,l-與meso-CB-PAO混合物進行同樣測試，發現meso-不純物依50 %、33.3 %、20 %遞減， d,l-型之繞射峰強度由1236.01，2486.6，3545.85呈一線性比例關係遞增。由以上初步結果顯示，配合DSC以XRPD法作為d,l-CB-PAO非鏡像立體異構物之立體化學純度評估，在定性與定量方面不失為一可行的方法。
關鍵字：非鏡像立體異構物，立體化學純度，微差掃描卡計，X光粉末繞射，核醫藥物
ASSESSMENT OF THE PURITY OF D,L-CB-PAO FROM
DIASTEREOISOMERIC MIXTURES USING XRPD METHOD
Chang-Shu Tsai
Department of Radiological Technology, Tzu-Chi College of Technology, 880, Sec. 2,
Chien-Kuo Road, Hualien, Taiwan 970, R. O. C.
E-mail address: fred@tccn.edu.tw
ABSTRACT
The diastereoisomers of CB-PAO were synthesized and d,l-CB-PAO, meso-CB-PAO and amorphous CB-PAO fractions were separated by repeated fractional recrystallization. Melting point measurement by using DSC was carried out very carefully. Attempt was made to use x-ray powder diffraction pattern method to evaluate the stereochemical purity of d,l-CB-PAO ligand. According to their characteristic of XRPD patterns, pure d,l-CB-PAO and meso-CB-PAO with fingerprints of 2 = 18.54 a ; d = 4.78 A and 2 = 10.87 a ; d = 8.13 A , respectively. For amorphous fraction it is 2 = 18.92 a ; d = 4.67 A. A series of mixture with the fixed ratios of 1:1, 2:1 and 4:1 with respect to d,l-isomers and meso- isomers were prepared and their XRPD pattern were recorded. It was observed from the XRPD patterns that the impurity of meso-CB-PAO decreased by 50 %, 33.3 %, and 20 %, respectively; and the peak intensities, for the d,l-CB-PAO increased linearly as observed with the figures 1236.06, 2486.6 and 3545.85. It seemed that XRPD method is qualitatively and quantitatively feasible for the assessment of the purity of d,l-CB-PAO from diastereoisomeric mixtures.
Key words: diastereoisomer, stereochemical purity , differential scanning calorimetry ( DSC ) , x-ray power diffraction ( XRPD ) , radiopharmaceutical