Compatibility of Melphalan in Iodinated Contrast Media

Melphalan is used in selective ophthalmic artery infusion chemotherapy. In the procedure to catheterize the ophthalmic artery in selective ophthalmic artery infusion chemotherapy, the microcatheter is usually filled with an iodinated contrast medium. It is not known whether mixing of iodinated contrast medium with melphalan solutions promotes precipitation of melphalan during selective ophthalmic artery infusion chemotherapy. The objective of the present study was to examine the compatibility of melphalan and iodinated contrast medium. In the experiments, melphalan solutions were prepared with and without iodinated contrast medium (iohexol 300 mg Iodine/mL or ioversol 74%). Melphalan solution of clinically relevant concentration (0.45 mg/mL) in the absence of iodinated contrast medium was evaluated as a reference. The 0.45-mg/mL melphalan solution was diluted with iodinated contrast medium at 1:9 and 1:1 ratios to form solutions comprising iodinated contrast medium at 10% or 50% (v/v), and each was evaluated. The formation of particles was examined using filtration (pore size 0.45 µm) followed by high-performance liquid chromatography at four quarterly time intervals (15 min, 30 min, 45 min, and 60 min) over a 1-hour period after solution preparation. High-performance liquid chromatography analysis of microfiltered solutions did not reveal evidence of melphalan crystal formation over a 60-minute period for the solutions studied. The filtration studies suggest that mixing of the iodinated contrast medium with melphalan solutions does not result in significant melphalan precipitation.