DETERMINATION OF ELSAMITRUCIN (BMY-28090) IN PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH FLUORESCENCE DETECTION

The cytostatic agent Elsamitrucin is a new fermentation product active in a variety of in vivo tumor models of murine and human origin. To d etermine its pharmacokinetics during the clinical phase I trial, an HP LC procedure was developed and validated. Plasma samples were extracte d after addition of the internal standard, i.e. the analog Chartreusin . Urine samples were injected without extraction of the samples. Becau se of the wide concentration range of Elsamitrucin in the plasma sampl es two standard curves were used: up to 100 nM and from 100-1000 nM. R ecoveries of Elsamitrucin from plasma were 87% and 74% for concentrati ons lower and higher than 100 nM, respectively. The detection limits w ere 1 nM in plasma and 7.5 nM in urine at a signal-to-noise ratio of 3 . The accuracy ranged from 95-107% for plasma and from 96-104% for uri ne. The within-day precision was equal to or less than 4.8% and equal to or less than 2.8% in plasma and urine, respectively. The between-da y precision was equal to or less than 4.4% and equal to or less than 7 .1% in plasma and urine, respectively. The method proved to be suffici ently sensitive, specific and accurate for analysis of clinical sample s for pharmacokinetic purposes.