胃腸道局部作用結(jié)合劑通過(guò)在胃腸道內(nèi)干擾磷酸鹽、膽鹽、鉀鹽等特定分子的吸收，有效調(diào)節(jié)血清中磷、膽固醇、鉀等物質(zhì)的生理水平。由于此類藥物在體內(nèi)吸收極少甚至不吸收，不適合采用以藥動(dòng)學(xué)參數(shù)為終點(diǎn)的人體生物等效性研究，因此監(jiān)管機(jī)構(gòu)推薦采用溶出、結(jié)合、崩解等體外實(shí)驗(yàn)對(duì)其生物等效性進(jìn)行評(píng)價(jià)。磷酸鹽、膽鹽、鉀鹽的檢測(cè)方法多樣，在體外結(jié)合研究的實(shí)際檢測(cè)中，需根據(jù)需求選擇適宜方法并完成方法學(xué)驗(yàn)證，以確保研究結(jié)果的可靠性。綜述胃腸道局部作用結(jié)合劑體外結(jié)合研究的檢測(cè)方法與技術(shù)，重點(diǎn)探討分光光度法、離子色譜法、毛細(xì)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(zhì)譜法等磷酸鹽檢測(cè)方法的優(yōu)劣及關(guān)鍵檢測(cè)要點(diǎn)。

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(guó)家藥監(jiān)局化學(xué)藥品質(zhì)量研究與評(píng)價(jià)重點(diǎn)實(shí)驗(yàn)室資助項(xiàng)目（2025HYZX06）