title: Development of a simple method for predicting the levels of di(2-ethylhexyl) phthalate migrated from PVC medical devices into pharmaceutical solutions.
abstract: This study deals with the development of a simple method for predicting the elution levels of di-2-ethylhexyl phthalate (DEHP) from medical devices made of polyvinyl chloride (PVC) by using the physicochemical properties of pharmaceutical injections as a marker. GC-MS analysis showed that the release of DEHP from medical grade PVC product was concentration-dependently increased by extraction with two kinds of lipophilic injections (Sandimmun and Prograf) and three kinds of surfactants (HCO-60, Tween 80, and SDS). The solubility of lipophilic pigments such as Sudan III, methyl yellow, and 1,4-diamino-anthraquinone against these solutions were also increased in a concentration-dependent manner, in which methyl yellow showed the highest response regarding the increase of optical density (O.D.). Further, electrical conductivity and static contact angle to the PVC sheet of the solutions were also increased or decreased in the same manner. As a result of the comparative study, significant correlation was found between DEHP release levels and these three physicochemical properties, particularly methyl yellow solubility, of the solutions tested. To evaluate the relationship in detail, DEHP release levels from PVC tubing and methyl yellow solubility of 53 injections used in gynecologic and obstetric fields were determined. None of the hydrophilic medicines showed any significant release of DEHP, and all showed low solubility of methyl yellow. On the other hand, the lipophilic medicines releasing a large amount of DEHP showed high solubility of methyl yellow (greater than O.D. 0.8). These results indicate that a significant proportional relationship exists between DEHP release potency and methyl yellow solubility of pharmaceutical solutions, and the risk of DEHP exposure to the patients administered pharmaceuticals through transfusion set could be easily predicted by the solubility test without complicated elution tests of DEHP using GC-MS or LC-MS.
authors.affiliation: Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. haishima@nihs.go.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haishima
authors.forename: Fumie
authors.initials: F
authors.lastname: Seshimo
authors.forename: Tae
authors.initials: T
authors.lastname: Higuchi
authors.forename: Haruko
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Chie
authors.initials: C
authors.lastname: Hasegawa
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Izumi
authors.forename: Tsunehisa
authors.initials: T
authors.lastname: Makino
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakahashi
authors.forename: Rie
authors.initials: R
authors.lastname: Ito
authors.forename: Koichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Saito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagami
authors.forename: Toshie
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakazawa
mesh_terms: D004051:Diethylhexyl Phthalate / Q000032:analysis*; D004340:Drug Contamination; D004864:Equipment and Supplies; D008401:Gas Chromatography-Mass Spectrometry; D007267:Injections; D011143:Polyvinyl Chloride / Q000737:chemistry*; D018570:Risk Assessment; D012995:Solubility; D012996:Solutions
chemical_list: D012996:Solutions; D011143:Polyvinyl Chloride; D004051:Diethylhexyl Phthalate