title: Contamination of syringe plungers during the sampling of cyclophosphamide solutions.
abstract: The presence of cytotoxic agents in the urine of operators and in their environment has been demonstrated. The pharmacokinetics of the urinary elimination of cyclophosphamide suggests that these drugs are absorbed cutaneously during handling. In the framework of a more general study on the contamination of hospital environment, the present study addresses the possible presence of cytotoxic agents on the plungers of syringes. The report is based on results indicating that the bacterial contamination of a plunger may result in the contamination of the solution being sampled. The study was divided into two phases. The first phase consisted in measuring the contamination of the plungers of eight syringes used for handling cyclophosphamide. Cyclophosphamide was analysed by gas chromatography-mass spectrometry with a detection limit of 0.1 ng/ml. The aim of the second phase was to localize the contamination on the plunger and thus determine the amount of drug that comes into contact with the gloves of the operators. The contamination was quantified by measuring the activity of metastable technetium. The results of the first phase showed that all the plungers were contaminated with cyclophosphamide amounts varying from 3.7 to 445.7 ng. The second phase showed that the infiltration of liquid onto the plunger depended on the solution being sampled. Almost no infiltration was seen with labelled water, but contamination appeared after the first sampling of a cyclophosphamide solution, then increased as a function of the number of times the plunger was pushed in and out. These results indicate that cyclophosphamide solutions infiltrate onto the plungers of syringes. They suggest that the general procedure for handling cytotoxic agents should be modified, and a regular replacement of syringes should be enforced. They also partly explain why the gloves of 50-90% operators are contaminated after a single preparation. The contamination seems to depend on the type of solution sampled and the number of samplings. Initial investigations by the manufacturer of the syringes had shown that the acid pH of cyclophosphamide solutions may affect the lubricant of the joint. Our study demonstrates that the contamination of plungers is one of the sources of environmental contamination for health workers handling antineoplastic agents, even in the absence of manipulation errors. More generally, these results demonstrate that the exposure of operators cannot be clearly described unless all existing sources of contamination in their environment are identified. The implementation of suitable procedures should thus take into account all possible sources of contamination, including technical facilities such as the use of a safety cabinet or an isolator.
authors.affiliation: Pharmacy Department, Centre Régional de Lutte Contre le Cancer Léon Bérard, 28 rue Laennec, 69373 Lyon Cedex 08, France. favier@lyon.fnclcc.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Favier
authors.forename: Laurence
authors.initials: L
authors.lastname: Gilles
authors.forename: Jean François
authors.initials: JF
authors.lastname: Latour
authors.forename: Michel
authors.initials: M
authors.lastname: Desage
authors.forename: Francesco
authors.initials: F
authors.lastname: Giammarile
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis*; D003520:Cyclophosphamide / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry; D013058:Mass Spectrometry; D016273:Occupational Exposure / Q000032:analysis; D019999:Pharmaceutical Solutions; D013594:Syringes; D013667:Technetium / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D019999:Pharmaceutical Solutions; D013667:Technetium; D003520:Cyclophosphamide