采用新型混合模式离子交换柱HPLC-ELSD法测定头孢曲松钠中钠离子含量以及成盐率

Determination the content of sodium and salt-forming rate in ceftriaxone sodium for injecion by an HPLC-ELSD method using a new type of mixed-mode ion exchange column

目的采用新型混合模式离子交换柱建立新的HPLC-ELSD法测定注射用头孢曲松钠中钠离子含量并计算成盐率。方法采用HPLC-ELSD法，采用新型混合模式离子交换柱Acclaim TrinityPl（100mm×3．0mm，5μm），以30mmol／L醋酸铵缓冲液（取醋酸铵4．59g，加水1900mL使溶解，用冰醋酸调节pH至5．21，加入乙腈100mL）-乙腈（50：50）为流动相，流速为0-3mL／min，柱温为25℃；蒸发光散射检测器的漂移管温度为90℃，氮气作为载气，流速为2．6mL／min；分析5批注射用头孢曲松钠、6批头孢曲松钠原料中钠离子含量以及成盐率，并进行了方法学验证。结果在此色谱条件下，可能存在的其他离子如Li＋、K＋、CI-以及质子化三嗪杂环与钠离子基线分离，在2．990～59．80μg／mL范围内，钠离子浓度与峰面积呈二项式相关关系（r=0．9990），加样回收率分别为110．0％、104．1％、107．1％，RSD分别为9．0％、1．7％、4．6％（n=3）。结论所建立的HPLC-ELSD法专属性强、线性范围宽、精密度较好、准确度高、耐用性好，可用于测定头孢曲松钠离子含量并优化成盐生产工艺。

Objective To build a new HPLC-ELSD method to determine the content of sodium and salt- forming rate in ceftriaxone sodium using a new type of mixed-mode ion exchange column. Methods The content of sodium and salt-forming rate in 5 lots of ceftriaxone sodium for injection and 6 lots of ceftriaxone sodium were analyzed using a new HPLC-ELSD method which was equipped with a new type of mixed-mode ion exchange column named as Acclaim Trinity P1 （3.0mm× 100mm, 5μm） and an ELSD detector using a mixture of 30mmol/L ammonium acetate buffer （weigh 4.59g of ammonium acetate, dissolve in 1900mL of water and adjust pH value to 5.21 with glacial acetic acid, add 100mL of acetonitrile）- acetonitrile（50：50） as mobile phase and the flow rate was 0.3mL/min. The column temperature is 25℃. The temperature of drift tube in an evaporating light scattering detector was 90℃. Nitrogen gas was used as carrier gas and the flow rate was 2.6mL/min. The method was validated adequeatly. Results Other ions which maybeexisted in ceftriaxone API were separated from sodium in the above chromatographic condition. The concentration of sodium was binomial related with the peak area from 2.990μg/mL to 59.80μg/mL. The spiked recoveries were 110.0%, 104.1%, 107.1% and the RSDs were 9.0%, 1.7%, 4.6%（n=3）. Coneluslon The HPLC-ELSD method is simple, specific, linear, accurate, moderate precise and robust to determine the content of sodium in ceftriaxone API and optimize the salt-forming process.