P1-28-3A SIMPLE AND RAPID HPLC METHOD FOR THE DETERMINATION OF MITOTANE IN HUMAN PLASMA AND A CASE OF ADRENAL CANCER

Abstract Background: Mitotane is used for the treatment of adrenal cancer and inoperable Cushing's syndrome. Previous studies show that monitoring of the plasma mitotane level is important for increasing efficacies and reducing adverse events such as digestive symptoms. Plasma concentration of 14 ∼ 20 µg/ml are considered therapeutic level. Case: A 72-year-old female was diagnosed as having adrenal cancer 30 years ago. She received left adrenalectomy, followed by repeated surgical resections of the recurrent diseases at left kidney, liver, left lung, diaphragm, transverse colon, para-aortic lymph node and abdominal cavity. Since developing unresectable metastasis, she decided to receive mitotane. To determine the optimal administration dose of mitotane, plasma concentration was analyzed. Informed and written consent was obtained from the patient and the pharmacokinetic study was approved by an institutional review board of Fukuoka University Hospital. Methods: A simple and highly sensitive high-performance liquid chromatographic method was developed for the determination of mitotane in human plasma. Mitotane and 2,2-diphenylpropane as an internal standard were extracted from plasma with ethyl acetate. They were separated by a J'sphere ODS-H80 column with a mixture of methanol-acetonitrile- water (81:6:13, v/v/v) as a mobile phase, and were then detected with a UV detector at 210 nm. The intra-day and inter-day variations for mitotane were reliable. Results: Plasma concentration of mitotane at steady-state for 1000, 3000 and 4500 mg daily doses were 1.60 ∼ 3.05, 4.98 ∼ 8.86 and 7.31 ∼ 9.48 µg/ml, respectively. Conclusions: The method is very simple, rapid, sensitive and selective for mitotane, and may therefore be useful as a routine analysis for the therapeutic drug monitoring of mitotane. The approach is able to provide therapeutic mitotane concentration and avoid the adverse events.