LHRH拮抗剂-CMC复合物的鉴别及含量测定

Preparation Identification and Determination of LHRH Antagonist-CMC Complex

目的制备促黄体生成激素释放激素（LHRH）拮抗剂LXT-101与羧甲基纤维素钠的不溶性复合物，对形成的复合物进行鉴别，并测定其中多肽的含量。方法分别将LXT-101和羧甲基纤维素钠制成水溶液，混合制成不溶性复合物；采用DSC法对复合物进行鉴别，并以HPLC法测定了复合物中多肽的含量和不同溶媒中的溶解度。结果复合物、物理混合物和药物及辅料的DSC图谱明显不同；复合物中多肽含量达80％；以5％醋酸溶液作为多肽和复合物的溶解介质，在10～80μg·ml^-1范围内，峰面积与药物浓度呈良好线性关系，r=0．9999；平均回收率99．8％，精密度RSD为0．54％；复合物的溶解度比原药明显降低。结论药物与羧甲基纤维素钠之问确已形成复合物；复合物在水和磷酸盐缓冲液中的溶解度明显降低，有望进一步制成缓释制剂。

Aim To prepare and evaluate a complex combined by sodium carboxymethyl cellulose and a novel LHRH antagonist LXT-101. Methods The complex was prepared by mixing the aqueous solutions of LXT-101 and CMC-Na, and was confirmed by differential scan calorimeter （DSC）. The peptide content of the complex and solu- bility in various media were determined by HPLC. Results The DSC thermogram of the LXT-101-CMC complex was considerably different from that of LXT-101, Na-CMC and their physical mixture. The LXT-101-CMC complex showed a high drug-loading of 80% and a low solubility in deionized water and phosphate buffer solutions. The peak area of peptide in the complex was well linear to the concentration over the range of 10 -80μg·ml^-1, r = 0. 999 9 ,with a mean recovery 99.8%, RSD 0. 54%. Conclusion A complex could be formed between CMC-Na and LXT-101. Furthermore, it could be turned into a sustained release formulation for LXT-101.