PF-4989216在人工胃肠液中的稳定性研究

Stability Evaluation of PF-4989216 in Artificial Simulated Gastrointestinal Fluid

研究PF-4989216在人工模拟胃肠液中的稳定性,为其代谢稳定性研究提供一定的基础。采用RP-HPLC法测定PF-4989216在人工胃肠液放置0,0. 5,1. 0,1. 5,2. 0,3. 0,4. 0,6. 0 h后的含量,计算其降解剩余百分含量。结果表明PF-4989216质量浓度与峰面积在2. 5～160μg/m L(R2=0. 9995,n=7)呈良好线性关系,在37℃空白人工胃肠液(不加酶)及人工胃肠液中的降解剩余百分率大于86. 77%。PF-4989216在模拟人体胃肠道环境的溶液中很稳定,不会发生明显降解,不受胃蛋白酶和胰蛋白酶的影响。

The stability of PF-4989216 in artificial simulated gastrointestinal fluid was investigated and some foundation was made for its further metabolic stability study.RP-HPLC method was conducted to determine the degradation of the remaining percentage in the simulated gastrointestinal fluid after 0,0.5,1.0,1.5,2.0,3.0,4.0,6.0 h.The results revealed that PF-4989216 had good linearity in the concentration range of 2.5~160μg/mL(R 2=0.9995,n=7).PF-4989216 showed good stability under the conditions of artificial gastric juice and artificial intestinal juice(with or without enzyme) at 37℃.The percentage of degradation remaining was greater than 86.77%.It can be concluded that PF-4989216 had good stability in artificial gastrointestinal fluid.No obvious degradation was observed against pepsin and trypsin.