Determination of Mitotane (DDD) and Principal Metabolite by a Simple HPLC-UV Method and Its Validation in Human Plasma Samples

Mitotane (DDD) is prescribed in adrenocortical renal carcinoma. Its principal metabolite, dichlorodiphenylethene (DDE), can accumulate fat tissues and from a toxicological point of view, probably more interesting than the other metabolite dichlorodiphenylacetate (DDA). Therapeutic Drug Monitoring (TDM) DDD plasma concentrations required to combine therapeutic efficacy with acceptable toxicity. Therefore, we developed simple fast HPLC-UV method monitor after liquid–liquid extraction calibration samples, quality controls, anonymous samples unknown DDE concentrations. Samples were injected into an HPLC instrument peaks mitotane (DDD), aldrin (internal standard, IS) resolved by stationary phase C18 column (250 mm × 4.6 mm, 5 μm), maintained at 35 °C. Mobile phase, made water/acetonitrile (10/90, v/v), was pumped flow 1.0 mL/min, absorbance monitored wavelength 226 nm. Average recovery 95% for all analytes, linear both (r2 = 0.9988, range 1–50 mg/L) 0.9964, 1–40 mg/L). The values limit detection quantitation 0.102 0.310 mg/L 0.036 0.108 DDE, respectively. retention time DDD, IS 7.06, 9.42 12.60 min, successfully validated according FDA guidelines finally adopted routine TDM.