Endotoxin exists on the outer membrane of Gram-negative bacteria and poses risks to human health by triggering a series of immune responses. Therefore, its accurate detection is essential. The Limulus amoebocyte lysate (LAL) test is the most pharmacopeia-recognized and popular technique for endotoxin detection. Despite its wide industry adoption, the low endotoxin recovery (LER) phenomenon can compromise the LAL test's reliability. This review summarizes the possible reasons attributing to the LER phenomenon from three different perspectives: the endotoxin standards used in hold time study, protein active pharmaceutical ingredients, and excipients. Potential mechanisms and strategies to mitigate the LER phenomenon are also discussed as presented by different research groups.

中文翻译：

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内毒素回收率低及其对内毒素检测的影响

内毒素存在于革兰氏阴性菌的外膜，通过引发一系列免疫反应对人体健康构成威胁。因此，对其进行准确检测至关重要。鲎变形细胞裂解物 (LAL) 测试是药典最认可和流行的内毒素检测技术。尽管其广泛的行业采用，低内毒素回收 (LER) 现象可能会损害 LAL 测试的可靠性。本综述从三个不同的角度总结了导致 LER 现象的可能原因：保持时间研究中使用的内毒素标准品、蛋白质活性药物成分和赋形剂。不同研究小组还讨论了减轻 LER 现象的潜在机制和策略。