胃腸道局部作用結合劑通過在胃腸道內干擾磷酸鹽、膽鹽、鉀鹽等特定分子的吸收，有效調節(jié)血清中磷、膽固醇、鉀等物質的生理水平。由于此類藥物在體內吸收極少甚至不吸收，不適合采用以藥動學參數為終點的人體生物等效性研究，因此監(jiān)管機構推薦采用溶出、結合、崩解等體外實驗對其生物等效性進行評價。磷酸鹽、膽鹽、鉀鹽的檢測方法多樣，在體外結合研究的實際檢測中，需根據需求選擇適宜方法并完成方法學驗證，以確保研究結果的可靠性。綜述胃腸道局部作用結合劑體外結合研究的檢測方法與技術，重點探討分光光度法、離子色譜法、毛細管電泳法、電感耦合等離子體發(fā)射光譜法及電感耦合等離子體質譜法等磷酸鹽檢測方法的優(yōu)劣及關鍵檢測要點。

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

國家藥監(jiān)局化學藥品質量研究與評價重點實驗室資助項目（2025HYZX06）