title: A simple HPLC method for plasma level monitoring of mitotane and its two main metabolites in adrenocortical cancer patients.
abstract: Mitotane (o,p'-DDD or (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane, DDD) is the drug of choice for non-resectable and metastatic adrenocortical carcinomas (ACC). Measurement of mitotane and metabolites, o,p'-DDE (1,1-dichloro-2-[p-chlorophenyl]-2-[o-chlorophenyl]ethene, DDE) and o,p'-DDA (1,1-[o,p'-dichlorodiphenyl] acetic acid, DDA) provides a better understanding of mitotane pharmacokinetics and pharmacodynamics. We have developed a simple, robust and efficient high performance liquid chromatography (HPLC) method to measure mitotane and its two main metabolites, DDE and DDA. The method involves a single ethanol extraction of mitotane, DDE, DDA, and an internal standard (int std) p,p'-DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane) with an extraction efficiency of 77-88%. All compounds are measured simultaneously using a reversed-phase phenyl HPLC column with an isocratic elution of mobile phase at a flow rate of 0.6 ml/min followed by UV detection at λ 226 nm. Inter and intra-day validation demonstrates good reproducibility and accuracy. Limits of quantitation are 0.2 μg/ml for mitotane and DDE, and 0.5 μg/ml for DDA. The method has been evaluated in plasma from 23 patients on mitotane therapy, revealing DDA concentrations 1-18 times higher than the parent compound.
authors: Department of Medical Oncology, Calvary Mater Newcastle Hospital, Locked Bag 7, Hunter Regional Mail Centre, NSW 2310, Australia.
authors: Madhu B
authors: MB
authors: Garg
authors: Jennette A
authors: JA
authors: Sakoff
authors: Stephen P
authors: SP
authors: Ackland
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008939:Mitotane / Q000097:blood* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008939:Mitotane