HPLC法拆分(-)-2(S)-苄基-4-酮-4-(顺式-全氢化异吲哚-2-基)丁酸钙对映体

目的：建立刺激胰岛素分泌的新型降糖药物(-)-2 (S)-苄基-4-酮-4-(顺式-全氢化异吲哚-2-基)丁酸钙对映体的HPLC拆分方法。方法：采用Sumichiral OA-3300手性柱(250 × 4.6 mm I.D., 5 μm), 柱温35℃，以0.05 mol·L-1醋酸铵的甲醇溶液为流动相，检测波长为210 nm。结果：本品两对映体在22分钟内实现良好分离，分离度达3以上，S－异构体分别在0.028 ~ 5.6 μg mL-1和0.03 ~ 6.0 μg mL-1范围内线性关系良好，回归方程分别为：Y=1.32×103x-2.54 (r=0.9997)和Y=1.15×103x-1.78 (r=0.9998)，最低检测限分别为0.15 ng和0.10 ng，方法精密度RSD低于1.0% (n=5)。结论：建立的对映体分离方法可用于本品光学异构体的质量控制。

Chiral Separation of Calcium (−)‐2(S)‐2‐Benzyl‐4‐oxo‐4‐(cis‐hexahydro‐2‐isoindolinyl)butyrate Enantiomers by High‐performance Liquid Chromatography

A chiral high‐performance liquid chromatographic method was developed for the enantioseparation of a new insulinotropic drug of the glinide class with rapid onset. The chiral separation was performed on a Sumichiral OA‐3300 column (250 mm×4.6 mm, 5 µm) with methanol containing 0.05 mol/L ammonium acetate as the optimized mobile phase at detection wavelengh 210 nm. Baseline separation of the two enantiomers was obtained in 22 min with a resolution of 3.01. Calibration graphs were constructed in a range of 0.028–5.6 µg·mL^?1 for S‐ and 0.03–6.0 µg·mL^?1 for R‐(?)‐enantiomer, respectively. The linear correlation equations are: y=1.32×10³x?2.54 (r=0.9997) for S‐enantiomer and y=1.15×10³x?1.78 (r=0.9998) for R‐enantiomer, respectively. The limits of detection obtained by S/N=3 were 0.15 ng for S‐ and 0.10 ng for R‐enantiomer, respectively. RSD of the method was below 1.0% (n=5).