Comparative evaluation of pyrogens tests in pharmaceutical products

Brazilian Journal of Microbiology

Rosimar L. Silveira¹  Simone S. Andrade¹  Cleber A. Schmidt¹  Renata G. Casali¹  Sérgio L. Dalmora¹ 

[1] ,Universidade Federal de Santa Maria Centro de Ciências da Saúde Departamento de Farmácia IndustrialSanta Maria RS ,Brasil

关键词: bacterial endotoxin;    Limulus amoebocyte lysate;    pyrogens;    rabbit pyrogen test;    endotoxinas bacterianas;    lisado do amebócito do Limulus;    pirogênios;    hipertermia em coelhos;   

DOI  :  10.1590/S1517-83822004000100007

来源: SciELO

【 摘 要 】

A comparison of methodologies for detection of pyrogens in pharmaceutical products was performed. The rabbit pyrogen test was optimized and the dose-response curve was obtained for the 2nd International Standard for bacterial endotoxins, establishing 13.81 EU/mL/kg as the concentration of endotoxin necessary to induce a temperature rise of 0.5ºC. The 0.5ºC cut-off was shown to give results that were more compatible with the pyrogenic doses for humans. The Limulus amoebocyte lysate test (LAL) was standardized with gel-clot and chromogenic endpoints, and used for the comparative evaluation of pharmaceutical products showing good agreement. The use of beta-glucan-reactive and non-reactive LAL reagents identified some products with false-positive results. The interference test was carried out and the specifications validated for some new products as the maximum valid dilution. The results emphasized the importance and limitations of the assays recommended for the evaluation of purity and quality control of parenteral medicinal products, improving the existing methodologies in the context of reduction and replacement in the use of animal models.

【 授权许可】

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