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-mPEG_(2000)...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-mPEG_(2000) 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.展开更多
The pyrogen test is an important index of quality management relating to druggery injection and instillation and the current common methods are domestic rabbit test and Bacterial Endotoxins Test. Since there are short...The pyrogen test is an important index of quality management relating to druggery injection and instillation and the current common methods are domestic rabbit test and Bacterial Endotoxins Test. Since there are shortcomings and limitations of resources in these two methods , it’s necessary to look for another new substitute. We have done the preliminary study of the feasibility of the pyrogen test with domestic rabbit’s blood plasm, human’s plasm and THP 1. The principle is as follows: after incubating the standard sample of bacterial endotoxins, glycogen anti coagulation whole blood extracting from the healthy domestic rabbit, extralin anti congealable whole blood from healthy volunteers, THP 1 cells together, measure the releasing amount of TNF and IL 6 from cell gene by the method of ELISA as a endogenesis index judging the pro heat role of endotoxin. The results indicate: the blood rabbit’s whole blood, human’s whole blood, or THP 1cell, their releasing amount of TNF and IL 6 are closely connected with the amount of acting endotoxins within a certain range. Three methods have their own peculiarities and some feasibilities as a new substitute method for pyrogen test with domestic rabbit.展开更多
基金supported by the National Natural Science Foundation of China [Grant No. 31600812]Strategic Priority Research Program of the Chinese Academy of Sciences [Grant No. XDA09030301]+1 种基金Natural Science Foundation Key Project [Grant No. 31630027, 31430031]the National Distinguished Young Scholars Grant [Grant No. 31225009]
文摘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-mPEG_(2000) 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.
文摘The pyrogen test is an important index of quality management relating to druggery injection and instillation and the current common methods are domestic rabbit test and Bacterial Endotoxins Test. Since there are shortcomings and limitations of resources in these two methods , it’s necessary to look for another new substitute. We have done the preliminary study of the feasibility of the pyrogen test with domestic rabbit’s blood plasm, human’s plasm and THP 1. The principle is as follows: after incubating the standard sample of bacterial endotoxins, glycogen anti coagulation whole blood extracting from the healthy domestic rabbit, extralin anti congealable whole blood from healthy volunteers, THP 1 cells together, measure the releasing amount of TNF and IL 6 from cell gene by the method of ELISA as a endogenesis index judging the pro heat role of endotoxin. The results indicate: the blood rabbit’s whole blood, human’s whole blood, or THP 1cell, their releasing amount of TNF and IL 6 are closely connected with the amount of acting endotoxins within a certain range. Three methods have their own peculiarities and some feasibilities as a new substitute method for pyrogen test with domestic rabbit.
