高效液相色谱法测定阿托伐他汀钙中间体L1的相关物质

Content Determination of Related Substances of Atorvastatin Calcium Intermediate L1 by HPLC

目的 建立高效液相色谱法测定阿托伐他汀钙中间体L1的有关物质.方法 采用Agilent Poroshell EC-C18色谱柱（100 mm＆#215;4.6 mm,2.7 μm）,以水∶乙腈∶四氢呋喃∶甲醇（36∶8.4∶29∶26.6,为流动相,流速为0.7 mL·min-1,检测波长为246 nm,柱温为30℃.结果 阿托伐他汀钙中间体L1和已知杂质L1-双胺、L1-脱氟、L1-R,S、L1-双氟互相之间分离度良好,L1-双胺在0.124 1～1.488 0μg·mL-1的浓度范围内呈良好的线性关系（R2=0.999 5,n=7）,L1-脱氟在0.386 6～3.093 0μg·mL-1的浓度范围内呈良好的线性关系（R2=1,n=6）,L1-R,S在0.357 1 ～2.856 0 μg· mL-1的浓度范围内呈良好的线性关系（R2 =0.999 0,n=6）,L1-双氟在0.187 3 ～ 1.498 0μg·mL-1的浓度范围内呈良好的线性关系（R2=0.999 3,n=6）,各杂质的控制限度均达到定量限.结论 该方法各杂质及中间体L1互相之间分离度良好,方法准确、可靠.

Objective To establish a high performance liquid chromatography （HPLC） method for determination of therelated substances of atorvastatin intermediate L1. Methods The chromatographic separation was performed on AgilentPoroshell EC-C18 column （100 mm伊4. 6 mm, 2. 7 μm） with the mobile phase consisting of H2 OACNTHFMeOH （368. 42926. 6）. The flow rate was 0. 7 mL·min-1 , the detection wavelength was 246 nm, and the column temperature was30 益. Results The method achieved good separation between L1 and its related impurites including L1-defluorination, L1-R,S, and L1-diamination. The linear range was 0. 124 1 - 1. 488 0 μg · mL-1 （ R2 = 0. 999 5, n = 7）, 0. 386 6 -3. 093 0 μg·mL-1 （R2 =1, n =6）, 0. 357 1-2. 856 0 μg·mL-1（R2 =0. 999 0, n = 6）, and 0. 187 3-1. 498 0 μg·mL-1（R2 =0. 999 3,n =6） for L1-diamination, L1-defluorination, L1-R,S, and L1-difluorination, respectively. The specifications ofeach impurity all reached the LOQ. Conclusion L1 separates well with the impurities. The method is accurate and reliable.