常用注射剂中依地酸二钠添加量合理性评估

Rationality evaluation of disodium edetate additive amount in commonly used injections

目的:采用UPLC-MS/MS法对常用注射剂中依地酸二钠添加量合理性进行评估。方法:采用安捷伦Infinity Lab Poroshell 120 HILIC-Z(3.0 mm×100 mm, 2.7μm),以20 mmol·L^(-1)乙酸铵溶液和乙腈为流动相,梯度洗脱,负离子多反应监测模式,建立快速测定注射液中依地酸二钠添加量的方法,并检测对比5种常用注射剂各生产企业产品与参比制剂中依地酸二钠的添加量差异。结果:盐酸多巴胺注射液参比制剂中不含依地酸二钠,2个生产企业产品中均含;维生素C注射液除一生产企业生产的2种规格不含依地酸二钠外,其余各生产企业产品均含,且含量差异较大;注射用奥美拉唑钠(静脉推注型)参比制剂与仿制生产企业产品均不含依地酸二钠;注射用奥美拉唑钠(静脉滴注型)参比制剂与各生产企业产品均含依地酸二钠,每瓶添加量为0.8~1.7 mg;注射用艾司奥美拉唑钠参比制剂与各生产企业产品均含依地酸二钠,每瓶添加量约为1.5 mg。注射用泮托拉唑钠参比制剂与各生产企业产品均含添加量,每瓶添加量为1.0~1.4 mg。结论:常用注射剂中依地酸二钠添加量差异较大,其合理性有待进一步提升。

OBJECTIVE To evaluate the rationality of disodium edetate additive amount in commonly used injections by UPLC-MS/MS.METHODS Agilent Infinity Lab Poroshell 120 HILIC-Z(3.0 mm×100 mm, 2.7 μm) chromatographic column was used for the separation with gradient elution of 20 mmol·L^(-1)ammonium acetate solution and acetonitrile as the mobile phase. A negative ion multi reaction monitoring mode was used to establish a method for the rapid determination of disodium edetate in injections. The content differences of disodium edetate in the products from five common injection manufacturers and the reference preparations were detected and compared by the method.RESULTS The reference preparation of dopamine hydrochloride injection did not contain disodium edetate, but the two preparations tested this time both contained disodium edetate. Except the two specifications produced by one manufacturer, the vitamin C injection produced by other manufacturers contained disodium edetate and the content was various significantly. Disodium edetate was not detected in the reference preparation and the products of imitation manufacturer of omeprazole sodium for injection(intravenous injection type). The reference preparation and the products of various manufacturers of omeprazole sodium for injection(intravenous drip type) contained disodium edetate, and the additive amount was between 0.8 and 1.7 mg in each bottle. The content of disodium edetate in esomeprazole sodium for injection produced by various manufacturers was the same as that of the reference preparation, which was about 1.5 mg in each bottle. The reference preparation and the products of various manufacturers of pantoprazole sodium for injection contained disodium edetate with the additive amount of 1.0-1.4 mg in each bottle.CONCLUSION The additive amount of disodium edetate in commonly used injections varies greatly, and its rationality needs to be further improved.