- Title
- A simple HPLC method for plasma level monitoring of mitotane and its two main metabolites in adrenocortical cancer patients
- Creator
- Garg, Madhu B.; Sakoff, Jennette A.; Ackland, Stephen P.
- Relation
- Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences Vol. 879, Issue 23, p. 2201-2205
- Publisher Link
- http://dx.doi.org/10.1016/j.jchromb.2011.06.001
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2011
- Description
- 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 λ226nm. Inter and intraday validation demonstrates good reproducibility and accuracy. Limits of quantitation are 0.2μg/ml for mitotane and DDE, and 0.5μg/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.
- Subject
- adrenocortical cancer; mitotane; metabolites; HPLC
- Identifier
- http://hdl.handle.net/1959.13/936528
- Identifier
- uon:12336
- Identifier
- ISSN:1570-0232
- Language
- eng
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