title: In vitro pyrogen test for toxic or immunomodulatory drugs.
abstract: Pyrogenic contaminations of some classes of injectable drugs, e.g. toxic or immunomodulatory as well as false-positive drugs, represent a major risk which cannot yet be excluded due to the limitations of current tests. Here we describe a modification of the In vitro Pyrogen Test termed AWIPT (Adsorb, Wash, In vitro Pyrogen Test), which addresses this problem by introducing a pre-incubation step in which pyrogenic contaminations in the test sample are adsorbed to albumin-coated beads. After rinsing, the beads are incubated with human whole blood and the release of the endogenous pyrogen interleukin-1beta is measured as a marker of pyrogenic activity. Intentional contaminations with lipopolysaccharide were retrieved from the chemotherapeutic agents paclitaxel, cisplatin and liposomal daunorubicin, the antibiotic gentamicin, the antifungal agent liposomal amphotericin B, and the corticosteroid prednisolone at lower dilutions than in the standard in vitro pyrogen test. This represents a promising new approach for the detection of pyrogenic contamination in drugs or in drugs containing interfering additives and should lead to improved safety levels.
authors.affiliation: Biochemical Pharmacology, University of Konstanz, POB M668 78457 Konstanz, Germany.
authors.forename: Mardas
authors.initials: M
authors.lastname: Daneshian
authors.forename: Armin
authors.initials: A
authors.lastname: Guenther
authors.forename: Albrecht
authors.initials: A
authors.lastname: Wendel
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Sonja
authors.initials: S
authors.lastname: von Aulock
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000666:Amphotericin B / Q000737:chemistry; D002945:Cisplatin / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry; D004340:Drug Contamination; D004797:Enzyme-Linked Immunosorbent Assay; D005839:Gentamicins / Q000737:chemistry; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry*; D007375:Interleukin-1 / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D008863:Microspheres; D017239:Paclitaxel / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011239:Prednisolone / Q000737:chemistry; D011749:Pyrogens / Q000032:analysis* / Q000097:blood; D012709:Serum Albumin / Q000737:chemistry; D013682:Teichoic Acids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005839:Gentamicins; D007155:Immunologic Factors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D004364:Pharmaceutical Preparations; D011749:Pyrogens; D012709:Serum Albumin; D013682:Teichoic Acids; C068538:liposomal amphotericin B; C009900:lipoteichoic acid; D000666:Amphotericin B; D004317:Doxorubicin; D011239:Prednisolone; D017239:Paclitaxel; D002945:Cisplatin