胃肠道局部作用结合剂通过在胃肠道内干扰磷酸盐、胆盐、钾盐等特定分子的吸收，有效调节血清中磷、胆固醇、钾等物质的生理水平。由于此类药物在体内吸收极少甚至不吸收，不适合采用以药动学参数为终点的人体生物等效性研究，因此监管机构推荐采用溶出、结合、崩解等体外实验对其生物等效性进行评价。磷酸盐、胆盐、钾盐的检测方法多样，在体外结合研究的实际检测中，需根据需求选择适宜方法并完成方法学验证，以确保研究结果的可靠性。综述胃肠道局部作用结合剂体外结合研究的检测方法与技术，重点探讨分光光度法、离子色谱法、毛细管电泳法、电感耦合等离子体发射光谱法及电感耦合等离子体质谱法等磷酸盐检测方法的优劣及关键检测要点。

Locally-acting gastrointestinal binding agents are drugs that can effectively regulate the physiological level of serum (phosphorus, cholesterol, potassium, etc.) by interfering with the absorption of specific molecules (phosphate, bile salts, potassium salts, etc.) in the gastrointestinal tract. Due to their minimal or negligible absorption in vivo, these drugs are inappropriate for pharmacokinetic parameter-based bioequivalence studies. Consequently, regulatory agencies recommend adopting in vitro studies including in vitro dissolution test, in vitro binding studies, and disintegration test to evaluate bioequivalence. The detection methods for phosphates, bile salts, and potassium salts are diverse, it is crucial to select appropriate methods based on actual needs, conduct methodological validation, and then proceed with research to obtain reliable results. This review summarizes the detection methods employed in the in vitro binding studies of locally-acting gastrointestinal binding agents, with a focus on the advantages, limitations, and critical considerations of phosphate detection techniques, including spectrophotometry, ion chromatography, capillary electrophoresis, ICP-MS, and ICP-OES.

R917

国家药监局化学药品质量研究与评价重点实验室资助项目（2025HYZX06）