The validation of column-switching LC/MS as a high-throughput approach for direct analysis of di(2-ethylhexyl) phthalate released from PVC medical devices in intravenous solution

Health Canada reported recently that medical devices containing di(2-ethylhexyl) phthalate (DEHP) should not be used in the clinical treatment of infants, young boys, pregnant women, and nursing mothers. The risk assessment of DEHP released from PVC medical devices is an important issue for hospitalized patients. In this study, a simple, accurate, low-contamination and high-throughput analytical technique for the determination of DEHP in intravenous (IV) solution was developed using column-switching liquid chromatography/mass spectrometry (LC/MS) with an extraction mini-column. The sample preparation for on-line extraction involved simply mixing IV solution with internal standard as DEHP-d(4) in LC glass vials. The IV fat emulsion drug sample cannot be analyzed directly, hence this sample spiked with DEHP-d4 solution was extracted by hexane and measured by column-switching LC/MS yielding an average recovery of 92.2% (C.V. = 7.8%, n = 5). A linear response was found for a variety of drugs tested within the validated range of 0.1 or 0.5-10 mug/ml with correlation coefficients (r) greater than 0.99. These results suggest that this method can assay background exposure to DEHP released from PVC medical devices in the patients. The method was applied to various IV solution samples to establish the first screening method for DEHP released from medical devices with respect to their safety. (C) 2003 Elsevier Science B.V. All rights reserved.