LIQUID-CHROMATOGRAPHIC ANALYSIS OF MESNA AND DIMESNA IN PLASMA AND URINE OF PATIENTS TREATED WITH MESNA

We describe in this report an expedient and accurate liquid chromatogr aphic method for measurement of mesna and dimesna in plasma and urine. The separation of mesna and the internal standard (p-aminobenzoic aci d, IS) was achieved on a 10-mu m, 8 mm (i.d.) x 10-cm C-18-Resolve car tridge in conjunction with radial compression system. An aqueous solut ion of sodium citrate (0.1 M), tetrabutyl ammonium phosphate (0.001 M) , and triethylamine (1:10,000, vol/vol), adjusted to pH 5 with 85% pho sphoric acid was used at a flow rate of 2 ml/min as a mobile phase. Th e compounds were detected in the effluent electrochemically at +450 mV . After an appropriate amount of IS was added, the plasma sample (100 mu l or fraction thereof) was deproteinized with an equal volume of 0. 0825 M sulfuric acid containing sodium hexametaphosphate (1.25% wt/vol ), whereas urine was diluted 1:50 with water and mixed 1:1 with an aqu eous solution of sodium hexametaphosphate (1.25% wt/vol). Dimesna was reduced back to mesna with sodium borohydride before analysis of the t otal mesna. The peak height ratio (drug/IS) varied linearly with the c oncentration, and the correlation coefficient was >0.992 for both mesn a and di mesna. The intrarun precision at different concentrations of mesna was equally good and the coefficient of variation was consistent ly <4.5%. No interference from endogenous substances or any concomitan tly used drug was observed. This assay is currently being used for mea surement of mesna and dimesna in plasma of bone marrow recipients who receive high doses of cyclophosphamide.