The in vitro loss of penicillamine in plasma, albumin solutions, and whole blood: Implications for pharmacokinetic studies of penicillamine

Abstract

The recent development of a high performance liquid chromatography assay method for the analysis of penicillamine in biological samples such as plasma, whole blood, and urine has provided a specific and sensitive assay method to aid in the study of penicillamine pharmacokinetics. Several investigators have reported measuring the plasma concentration of penicillamine. Some of these investigators have indicated that the plasma must be assayed immediately. However, such restrictions can limit the feasibility of a pharmacokinetic study. The results of this paper demonstrate the instability of penicillamine in plasma, albumin solutions, and whole blood. The rate of loss of penicillamine was shown to be influenced by the concentration of albumin. As a result of the significant loss of penicillamine over a short period of time, plasma or whole blood samples must be deproteinated immediately upon collection to avoid the loss of reduced penicillamine. Methods are presented for the preparation of biological samples so that the oxidation of penicillamine is prevented and the samples can be held for several days prior to analysis.