离子色谱法检测泮托拉唑钠原料药中硫酸二甲酯

Determination of dimethyl sulphate in pantoprazole sodium active pharmaceutical ingredient by ion chromatography

建立了一种准确测定泮托拉唑钠原料药中残留硫酸二甲酯含量的离子色谱方法.利用硫酸二甲酯可以完全水解为硫酸单甲酯的反应,样品经氢氧化钠溶液溶解后,采用离子色谱法,以氢氧化钾为淋洗液,阴离子抑制器条件下,采用电导检测器检测硫酸单甲酯含量,经计算实现准确测定硫酸二甲酯含量的目的.硫酸单甲酯的检测限低至7 ng·mL^(-1),在15 ng·mL^(-1)—5μg·mL^(-1)范围内呈良好的线性关系,相关系数(r)为0.9998,低、中、高浓度的加标回收率在87.5%—98.5%之间,定量限浓度溶液连续进样6次,相对标准偏差(RSD)为6.5%.该方法准确、灵敏度高、精密度好、成本低、操作简便快速,不仅可用于泮托拉唑钠原料药中硫酸二甲酯的含量测定,同时也为其他原料药和制剂中硫酸二甲酯含量测定提供了参考依据.

This study aimed to develop a strategy for the determination of dimethyl sulphate in pantoprazole sodium Active Principal Ingredient(API)employing ion chromatography(IC).API samples were first dissolved in sodium hydroxide solution.Then,methyl hydrogen sulphate was determined by IC in electric conductivity detector mode under the anion suppressor by using KOH solution as the eluent.Due to that dimethyl sulphate hydrolyzes to equivalent mole of methyl hydrogen sulphate,the concentration of dimethyl sulphate could be obtained by analyzing the methyl hydrogen sulphate concentration.The limit of detection was 7 ng·mL^(-1).The assay was linear over the concentration range of 15 ng·mL^(-1)to 5μg·mL^(-1)with a correlation coefficient(r)of 0.9998.The spiked recoveries were between 87.5%and 98.5%at three concentration levels(low,medium and high).The relative standard deviation(RSD)was 6.5%from six consecutive LOQ concentration analyses of the same sample.The method is accurate,sensitive,precise,and low cost with minimum sample preparation.It is not only a suitable approach for the determination of dimethyl sulphate in pantoprazole sodium API,but also a guideline for dimethyl sulphate quantification in other types of API and preparations.