A HIGH-PRESSURE LIQUID-CHROMATOGRAPHIC METHOD FOR MEASURING MITOTANE [1,1-(O,P'-DICHLORODIPHENYL)-2,2-DICHLOROETHANE] AND ITS METABOLITE 1,1-(O,P'-DICHLORODIPHENYL)-2,2-DICHLOROETHENE IN PLASMA

The adrenolytic agent mitotane [o,p'-DDD or 1,1-(o,p'-dichlorodiphenyl )-2,2-dichloroethane] has been employed in the nonsurgical treatment o f patients with adrenal carcinoma for several decades. Its use is hamp ered by serious side effects, which may be limited by analytically gui ded dose modifications in the individual patient. Mitotane analyses ha ve previously been undertaken by gas chromatography with electron capt ure detection, A sensitive high-pressure liquid chromatographic method for measuring mitotane in plasma is described, After protein precipit ation with 1.5 vol of acetone, mitotane and its metabolite 1,1-(o,p'-d ichlorodiphenyl)-2,2-dichloroethene (o,p'-DDE) are resolved by isocrat ic elution from a C-18 reversed-phase support and quantified by ultrav iolet detection at 230 nm. Recoveries of mitotane and o,p'-DDE after d eproteinization were quantitative. Within-run and between-day coeffici ents of variation were <4% over the entire therapeutic range. The limi t of detection was 0.25 mu mol/L and the standard curve was linear in the 1-100 mu mol/L range. The method has been evaluated using samples obtained from an adolescent girl who had metastatic adrenocortical car cinoma. Data from this single patient may suggest that systemic absorp tion of mitotane is adequate, and toxicity possibly decreased, when mi totane is administered by the rectal route.