PHYSICAL COMPATIBILITY OF MELPHALAN WITH SELECTED DRUGS DURING SIMULATED Y-SITE ADMINISTRATION

The physical compatibility of melphalan injection with selected drugs during simulated Y-site administration was studied. A 5-mL sample of melphalan 0.1 mg/mL in 0.9% sodium chloride injection was combined with a 5-mL sample of each of 91 drugs at concentrations used clinically. Each combination was prepared in duplicate, with the order of mixing reversed between the two. The samples were inspected visually in normal fluorescent light and in high-intensity light at zero, one, and three hours after preparation. A turbidimeter was used to measure the turbidity of each drug combination at the same intervals. Samples showing a change in the visually or turbidimetrically determined haze level were subjected to particle counting and sizing. None of the drug combinations resulted in visual evidence of precipitation, color change, or gas production. Most combinations had a measured turbidity of <0.1 nephelometric turbidity unit (NTU) and were compatible. A few combinations had turbidities of greater-than-or-equal-to 0.1 NTU, but the turbidity did not change over the study period and the combinations were considered compatible. Combinations of melphalan with methylprednisolone sodium succinate, prochlorperazine edisylate, or daunorubicin hydrochloride had a very small increase in turbidity but were compatible. Melphalan did not increase the doubling of turbidity that idarubicin hydrochloride shows upon simple dilution. Neither the total particle burden nor the number of particles of greater-than-or-equal-to 10 mum increased in any combination that was tested. However, combinations with amphotericin B or chlorpromazine hydrochloride showed large increases in measured turbidity and were incompatible. Melphalan 0.1 mg/mL in 0.9% sodium chloride injection was physically compatible with most of the drugs tested for up to three hours at 22-degrees-C. Exceptions were combinations with amphotericin B and with chlorpromazine hydrochloride.