Endotoxin testing of proteins for parenteral administration using the Mono Mac 6 assay.
BACKGROUND
Pharmaceutical products containing proteins cause problems in testing for endotoxin and pyrogens. Many proteins interfere with the LAL test and the proteins are immunogenic in rabbits. The monocytic cell line Mono Mac 6 is an alternative assay for detection of endotoxin and other pyrogens.


OBJECTIVE
To evaluate the use of the Mono Mac 6 assay for quantitative detection of endotoxin in proteins.


METHODS
The quantitative detection of endotoxin in the three pharmaceutical products human albumin, gamma-globulin and somatropin was evaluated.


RESULTS
For the three proteins the detection limit of the Mono Mac 6 assay was far below the threshold endotoxin limit described by the European Pharmacopoeia. Interference of two of the proteins with the Mono Mac 6 assay was observed, but the problems could be overcome either by dilution of the product or by comparison of the test with an endotoxin standard curve prepared in a solution of the respective pyrogen-free protein.


CONCLUSIONS
The Mono Mac 6 assay is a reliable method for quantitative detection of endotoxin in proteins.
Moesby
L
L
Department of Pharmacology, The Royal Danish School of Pharmacy, 2 Universitetsparken, 2100 Copenhagen, Denmark. LM@mail.dfh.dk
Hansen
E W
EW
Christensen
J D
JD
D000284:Administration, Oral; D000818:Animals; D001681:Biological Assay / Q000379:methods; D002460:Cell Line; D004340:Drug Contamination; D004731:Endotoxins / Q000032:analysis*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000592:standards*; D011506:Proteins; D011817:Rabbits; D012680:Sensitivity and Specificity
D004731:Endotoxins; D004364:Pharmaceutical Preparations; D011506:Proteins