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目的:探讨用混合模式离子交换柱建立HPLC-ELSD法测定化学药物成盐离子含量准确性的影响因素。方法:采用新型混合模式离子交换柱Acclaim Trinity P1(3.0 mm×100 mm,5μm),以30 mmol·L-1醋酸铵缓冲液(取醋酸铵4.59 g,加水1900 mL使溶解,用冰醋酸调节pH至5.2,加入乙腈100 mL)-乙腈(50∶50,v/v)为流动相,流速0.3 mL·min-1,柱温25℃;以蒸发光散射检测器检测,漂移管温度90℃,氮气作为载气,流速2.6 L·min-1。建立HPLC-ELSD法测定奥美拉唑钠中钠离子含量并进行方法学验证;同时选择奥美拉唑钠、头孢曲松钠、盐酸博宁霉素,分别代表药物分子在色谱过程中不保留、强保留和不洗脱3种状态,进行准确度、精密度试验,以数据统计软件SPSS 19.0进行统计分析,考察药物分子洗脱状态对成盐离子含量准确性(准确度、精密度)的影响。结果:钠离子浓度在1.94~77.48μg·mL-1范围内与峰面积呈二项式相关关系(r=0.9999);加样回收率(n=3)分别为104.5%、101.7%、102.6%,RSD分别为1.3%、3.7%、2.2%;奥美拉唑钠中钠离子平均含量(n=8)为6.23%,与理论钠离子含量(6.24%)无显著性差异(t-检验,α=0.05);药物分子洗脱状态对钠离子测定的中间精密度、重复性结果以及氯离子测定的重复性有影响(ANOVA分析,α=0.05),药物分子很难洗脱以及不洗脱将导致精密度偏低。结论:采用新型混合模式离子交换柱,用HPLC-ELSD法测定化学药物中成盐离子含量时,方法通用性好,专属性强,线性范围宽,耐用性好,但药物分子很难洗脱或者不洗脱在色谱填料上将导致精密度偏低。
OBJECTIVE: To investigate the factors influencing the accuracy of chemical salt formation by HPLC-ELSD with mixed mode ion exchange column. Methods: Acclaim Trinity P1 (3.0 mm × 100 mm, 5 μm) was mixed with 30 mmol·L-1 ammonium acetate buffer solution (4.59 g ammonium acetate and 1900 mL water) to dissolve and adjust with glacial acetic acid pH = 5.2, acetonitrile 100 mL) -acetonitrile (50:50, v / v) was used as the mobile phase at a flow rate of 0.3 mL · min-1 and the column temperature was 25 ℃. The detection was performed by evaporative light scattering detector. , Nitrogen as carrier gas, flow rate 2.6 L · min-1. To establish a method for the determination of sodium ion in omeprazole sodium by HPLC-ELSD and to validate the method. At the same time, omeprazole sodium, ceftriaxone sodium and brimminginomycin were chosen to represent that the drug molecules were not retained in the chromatographic process , Strong retention and no elution three kinds of state, the accuracy and precision tests, statistical analysis software SPSS 19.0 statistical analysis of the molecular elution of drugs on salt ion content accuracy (accuracy, precision) influences. Results: The sodium ion concentration showed a binomial correlation with the peak area in the range of 1.94-77.48μg · mL-1 (r = 0.9999). The recovery rates (n = 3) were 104.5%, 101.7% and 102.6% (RSD) were 1.3%, 3.7% and 2.2% respectively. The average content of sodium in omeprazole sodium (n = 8) was 6.23%, which was not significantly different from the theoretical sodium content α = 0.05). The influence of drug molecule elution status on the intermediate precision of sodium determination, reproducibility and repeatability of chloride ion determination (ANOVA analysis, α = 0.05), the drug molecule was difficult to elute and did not elute Will lead to low precision. CONCLUSION: The new mixed-mode ion exchange column has good generality, specificity, wide linear range and good durability when using HPLC-ELSD to determine the content of salt-forming ions in chemical drugs. However, the drug molecules are difficult to elute or Not elution on the chromatographic packing will lead to low precision.