LAL test and RPT for endotoxin detection of CPT-11/DSPE-mPEG2000 nanoformulation: What if traditional methods are not applicable?

• Main Authors: Yanan Jin, Juanjuan Jia, Chan Li, Jianqi Xue, Jiabei Sun, Kaiyuan Wang, Yaling Gan, Jing Xu, Yaqin Shi, Xingjie Liang
• Format: Article
• Language: English
• Published: Elsevier 2018-05-01
• Series: Asian Journal of Pharmaceutical Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1818087617307286
• ISSN: 1818-0876

Endotoxin detection is an important step in drug characterization. Herein we found that a chemotherapeutic drug nanoformulation composed of irinotecan hydrochloride (CPT-11) and an amphiphilic molecule DSPE-mPEG2000 can interfere with the limulus amebocyte lysate assay (LAL). Furthermore, the rabbit pyrogen test (RPT) results indicated that at a relatively high dosage, the drug irinotecan hydrochloride can induce a hypothermia effect which may render the RPT results ambiguous in determination of the safety of the drug formulation.Our findings demonstrate limitations of endotoxin detection in micellar drugs, and call for the necessity of developing reliable endotoxin detection methods that can overcome the interference of nanomaterials in order to better ensure the drug safety of patients in future pharmaceutical drug development. Keywords: Irinotecan hydrochloride, Endotoxin detection, Micelle, DSPE-mPEG2000, Limulus amebocyte lysate assay, Rabbit pyrogen test