注射用磷酸特地唑胺细菌内毒素检查

Study on Bacterial Endotoxin Test of Tedizolid Phosphate for Injection

目的:注射用磷酸特地唑胺用于特定的敏感细菌引起的成人急性细菌性皮肤和皮肤结构感染,被美国FDA批准磷酸特地唑胺上市,临床研究也进入了临床Ⅱ期,用于严重革兰氏阳性菌感染的治疗。该药尚未在中国上市。未被《中国药典》2015年版收录,亦没有与之相关的质量标准,本文建立了该药品的检验方法,以完善医药市场对药物的质量监管要求。方法:参照中国药典2015年版四部通则试验要求,拟定了质量标准,并对细菌内毒素的检查方法进行了方法学验证。结果:拟定本品的细菌内毒素限值为1.5 EU·mg^(-1),当采用灵敏度为0.5 EU·mL^(-1)的鲎试剂,样品浓度为含磷酸特地唑胺4 mg·mL^(-1)时,对内毒素与鲎试剂的反应无干扰。结论:当采用两个鲎试剂生产厂家的试剂对样品进行干扰试验,灵敏度为0.5 EU·mL^(-1),样品浓度为含磷酸特地唑胺4 mg·mL^(-1)时,对内毒素与鲎试剂的反应无干扰。此限值为可靠限值。

Objective： Tedizolid phosphate for injection has been approved by FDA for the acute bacterial skin and skin structure infections in adults caused by specific ans sensitive bacteria. However, it has not been approved in China, and is still at the stage of phase Ⅱ clinical study with target to the serious Gram-positive bacteria infection. So it is not listed into the monographs of ChP 2015, and has no the legal specification. The method for bacterial endotoxin test of Tedizolid Phosphate for injection was established as the drug supervision need. Methods： The method was established in compliance with general notice XI E the bacterial endotoxin test, Vol IV, ChP 2015 and validated. Results： The bacterial endotoxin limit of tedizolid phosphate for injection was set as 1.5 EU·mL^-1. When TAL with the sensitivity of 0. 5 EU·mL^-1 and 4 mg·mL^-1 tedizolid phosphate solution were adopted, there was no interference for reaction between endotoxin and TAL Conclusion： The TALs from two manufacturers was used for interference test. It was shown that there was no interference between reaction of endotoxin and TAL when 4 mg·mL^-1 tedizolid phosphate solution and TALs with the sensitivity of 0. 5 EU·mL^-1 was used. It is reliable to take 4 mg·mL^-1 tedizolid phosphate solution as the maximum non-interference concentration on the bacteria endotoxin test.