固相萃取-离子色谱法测定坎地沙坦酯原料药中叠氮化钠和四丁基溴化铵的残留量

Determination of Sodium Azide and Tetrabutylammonium Bromide Residues in Active Pharmaceutical Ingredients of Candesartan Cilexetil by Ion Chromatography with Solid Phase Extraction

将坎地沙坦酯原料药约100 mg用水超声提取15 min,离心10 min.取上清液过0.22μm滤膜,收集滤液,过预先活化好的C_(18)固相萃取小柱.洗脱液流入离子色谱仪,在IonPac AS18阴离子交换色谱柱上分离,柱温为35℃.以氢氧化钾溶液进行程序淋洗,以电导检测器进行检测.结果表明,N_(3)^(-)和Br^(-)与水中NO_(3)^(-)的分离度均大于1.50,原料药及溶剂水中其他杂质离子的干扰较小;N_(3)^(-)和Br^(-)的质量浓度在一定范围内与其对应的峰面积呈线性关系,检出限(3S/N)分别为0.00070,0.0014 mg·L^(-1);对空白样品进行3个浓度水平的加标回收试验,N_(3)^(-)和Br^(-)的回收率分别为88.2%~93.5%和101%~104%,测定值的相对标准偏差(n=6)分别为2.6%和0.55%;方法用于实际样品分析,取得了满意结果.

Candesartan cilexetil(about 100 mg)was extracted ultrasonically with water for 15 min and centrifuged for 10 min.The supernatant was passed through 0.22μm filter membrane,and the collected filtrate was passed through pre-activated C_(18) solid phase extraction cartridge.The eluent was flowed into the ion chromatograph and separated on IonPac AS18 anion exchange chromatographic column at 35℃of the column temperature.The programmed rinse was performed with potassium hydroxide solution,and the conductmetric detector was used for detection.As shown by the results,the resolutions of N_(3)^(-)-NO_(3)^(-)and Br^(-)-NO_(3)^(-)in water were both greater than 1.50,and the interference of other impurity ions in active pharmaceutical ingredients(API)and solvent water was smaller.Linear relationships between values of peak area and mass concentration of N_(3)^(-)and Br^(-)were found in definite ranges,with detection limits(3 S/N)of 0.00070 mg·L^(-1)for N_(3)^(-)and 0.0014 mg·L^(-1)for Br^(-),respectively.Test for recovery was made on the blank sample at 3 concentration levels by standard addition method,giving results in the range of 88.2%-93.5%and 101%-104%,respectively,with RSDs(n=6)of the determined values of 2.6%and 0.55%,respectively.The method was applied to the analysis of actual samples,and satisfactory results were obtained.