Leaching of diethylhexyl phthalate from multilayer tubing into etoposide infusion solutions

• Published in: American journal of health-system pharmacy 2005-01, Vol.62 (2), p.182-188
• Main Authors: Bagel-Boithias, Sandrine, Sautou-Miranda, Valerie, Bourdeaux, Daniel, Tramier, Violaine, Boyer, Anne, Chopineau, Jean
• Format: Article
• Language: English
• Subjects: Chromatography, High Pressure Liquid - methods; Diethylhexyl Phthalate - administration & dosage; Diethylhexyl Phthalate - chemistry; Disposable Equipment - standards; Disposable Equipment - statistics & numerical data; Drug Contamination; Drug Evaluation, Preclinical - methods; Etoposide - administration & dosage; Etoposide - chemistry; Infusion Pumps - standards; Infusion Pumps - statistics & numerical data; Infusions, Intravenous; Materials Testing - methods; Materials Testing - standards; Polyvinyl Chloride - administration & dosage; Polyvinyl Chloride - chemistry; Solutions - administration & dosage; Solutions - chemistry; Technology, Pharmaceutical - methods; Time Factors
• ISSN: 1079-2082; 1535-2900
• DOI: 10.1093/ajhp/62.2.182

The extent of leaching of diethylhexyl phthalate (DEHP) from various polyvinyl chloride (PVC), polyethylene (PE), coextruded (PVC and PE), and triple-layered (PVC, ethyl vinyl acetate, and PE) i.v. extension tubing into etoposide infusion solutions was studied. Different lengths of tubing (25, 50, and 80 cm) were tested in two types of experiments: (1) static, in which the etoposide solution was left in contact inside the tubing for various times and then removed, and chromatography was used to quantify the DEHP content of the effluate, and (2) dynamic, in which infusion was simulated using syringe reservoirs, and three flow rates were tested to assess the effect of flow rate on the quantities of DEHP leached. The static study showed that large quantities of DEHP were leached from all tubing types except the PE tubing. The dynamic study confirmed that leaching occurred, although the values were below the threshold limit of 5 microg/mL. The values varied depending on flow rate, tubing length, and etoposide concentration. The coextruded and triple-layered i.v. tubing did not provide the inertness and safety they are intended to have, as DEHP not only leached out but did so in quantities almost equivalent to those found with tubing made of PVC only. DEHP leached rapidly from PVC, coextruded, and triple-layered i.v. tubing into etoposide infusion solution. The quantity of DEHP found in the infusion solution was influenced by the length of the tubing and concentration of etoposide.