注射用哌拉西林钠舒巴坦钠有关物质检测标准的提高

The improvement of testing standards about related substances of piperacillin sodium and sulbactam sodium for injection

目的:建立高效液相色谱梯度法测定注射用哌拉西林钠舒巴坦钠的有关物质。方法:采用十八烷基硅烷键合硅胶为填充剂,流动相A为甲醇-水-0.2 mol·L-1磷酸二氢钠溶液-10%氢氧化四丁基铵溶液(550∶366∶82∶2),流动相B为水-0.2 mol·L-1磷酸二氢钠溶液-10%氢氧化四丁基铵溶液(447∶100∶3)[用磷酸、氢氧化钠调节p H至(5.50±0.02)],梯度洗脱,流速为1.0 m L·min-1,检测波长为220 nm,进样量为10μL。结果:本法可有效测定哌拉西林钠和舒巴坦钠中的有关物质,且降解产物和有关物质均达到较好分离,哌拉西林杂质A和舒巴坦杂质A分别在47.13~424.18μg·m L-1和10.51~94.59μg·m L-1之间线性良好,检测限分别为0.231 02和0.325 15μg·m L-1,对5个批次的本产品进行测定,各杂质可以有效检出。结论:本方法简便、快速、灵敏、专属性和耐用性好,可以用来测定注射用哌拉西林钠舒巴坦钠中有关物质。

Objective： To establish an HPLC gradient elution method for the determination of related substances of piperacillin sodium and sulbactam sodium for injection. Methods： The separation was achieved by using an ODS column with gradient elution. Mobile phase A was a mixture of methanol,water,0. 2 mol·L^-1 monobasic sodium phosphate,and 10% tetrabutylammonium hydroxide(550∶ 366∶ 82∶ 2） and mobile phase B was a mixture of water,0. 2 mol·L^-1 monobasic sodium phosphate,and 10% tetrabutylammonium hydroxide(447∶ 100∶ 3,p H adjusted to 5. 50 ± 0. 02 with phosphoric acid）. The flow rate was 1. 0 m L·min^-1. The UV wavelength was220 nm,and the injection volume was 10 μL. Results： The method could effectively detect related substances of piperacillin sodium and sulbactam sodium for injection. And piperacillin sodium and sulbactam sodium and their related substances were separated effectively by this method. The linearities of the calibration curves of piperacillin impurity A and sulbactam impurity A were good in the range of 47. 13 ～ 424. 18 μg·mL-1 and 10. 51 ～ 94. 59 μg·mL-1,respectively. The decetion limits were 0. 231 02 and 0. 325 15 μg·mL-1,respectively. Five batches of sample were determined. The related substances in piperacillin sodium and sulbactam sodium could be effectively determined. Conclusion： The HPLC method is easy,rapid,accurate,with good specificity and durability,which maybe used for the inspection of related substances in piperacillin sodium and sulbactam sodium for injection.