High-pressure liquid chromatographic analysis of melphalan in plasma.

A new sensitive and rapid high-pressure liquid chromatographic determination of melphalan in plasma was developed. Recovery of 1 microgram added to 1 ml of plasma at 23 degrees was 94% but was greatly reduced at higher temperature. The method has been applied to plasma determinations of melphalan in rats and humans and is currently being utilized for human pharmacokinetic studies.

Hydrolysis and protein binding of melphalan.

Melphalan (30 microgram/ml) is completely hydrolyzed in water at 37 degrees after 8 hr. At lower temperatures, hydrolysis proceeds at slower rates. The presence of bovine serum albumin retards hydrolysis of melphalan (30 microgram/ml) in water. The melphalan hydrolysis rate is directely releated to the bovine serum albumin concentration. At 37 degrees, 8 g of bovine serum albumin/100 ml of water gives a recovery rate of melphalan similar to that of human plasma. In vitro alkylation of melphalan at 37 degrees with human plasma containing 30 microgram/ml, calculated by equilibrium dialysis, methanol extraction, and high-pressure liquid chromatographic analysis, is 30% after 8 hr.