A Liquid Chromatographic Electrochemical Assay for S-2-(3-Aminopropylamino) Ethylphosphorothioate (WR2721) in Human Plasma

Abstract

A liquid chromatographic electrochemical method for the determination of the radioprotective drug WR2721 in human plasma has been developed. This method includes the use of a Hg/Au electrochemical detector for the direct measurement of WR2721 concentration. An analog of WR2721, S-3-{4-aminobutylamino} propylphosphorothioate (WR80855) is the internal standard. The retention times for WR2721 and WR80855 are approximately 4.5 and 9 minutes, respectively. WR1065, the free sulfhydryl metabolite of WR2721, is retained on the column under the described chromatographic conditions and therefore does not interefere with the determination of the parent drug. With modification of the mobile phase WR1065 is eluted from the column at a retention time of approximately 20 minutes. This method has good linearity, precision and accuracy, and is free from interference from endogenous plasma substances. Preliminary results showing the applicability of this method to human pharmacokinetic studies and to investigating the enzymatic hydrolysis of WR2721 are presented.