Determination of tris(2-ethylhexyl)trimellitate released from PVC tube by LC–MS/MS

Tris(2-ethylhexyl)trimellitate (TOTM) is used as an alternative plasticizer of polyvinyl chloride (PVC) medical devices. A method for the determination of TOTM released from PVC medical devices into intravenous preparations was developed, which uses liquid chromatography-tandem mass spectrometry (LC–MS/MS). A PVC tube was filled with an intravenous preparation and extraction was carried out by shaking for 1 h at room temperature. LC was performed with an Inertsil®-C8 (50 mm × 2.1 mm, 5 μm) column. The isocratic mobile phase was acetonitrile:purified water (90:10, v/v) at a flow rate of 0.2 ml/min. MS detection was accomplished with an MS/MS detector equipped with a turbo ionspray ionization source in the positive ion mode. The limit of detection and the limit of quantification for the standard solution of TOTM was 0.5 ng/ml (S/N = 3) and 1.0 ng/ml (S/N ≥ 10), respectively. When Prograf® (tacrolimus) was used, the average recovery of TOTM was 101.1% (R.S.D. = 4.72%; n = 3). When our method was applied to the determination of TOTM released from unsterilized and gamma-ray-sterilized PVC tubes, we found that a higher concentration of TOTM was released from the unsterilized PVC tube than from the gamma-ray-sterilized one.