A new simple HPLC method for measuring mitotane and its two principal metabolites Tests in animals and mitotane-treated patients.
A new C18 reversed-phase column and UV HPLC method for the detection of mitotane, its principal metabolites, dichlorodiphenylacetate and dichlrodiphenylethene, and its precursor DDT is described. In this article mitotane, dichlorodiphenylacetate, and dichlrodiphenylethene concentrations in organs of rats fed on a mitotane diet, and the effects of erythromycin and grapefruit juice as cytochrome P450 common inhibitors are presented. Tissue accumulation of mitotane and dichlrodiphenylethene, the acquired ability to eliminate dichlorodiphenylacetate, and inhibition of beta-hydroxylation by both inhibitors are illustrated here. Blood samples from mitotane-treated patients revealed two correlations: plasma mitotane/dichlrodiphenylethene and plasma mitotane/red cell mitotane.
De Francia
Sivia
S
Department of Clinical and Biological Sciences, Laboratory of Pharmacology, University of Turin, Ospedale San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy. silvia.defrancia@unito.it
Pirro
Elisa
E
Zappia
Franco
F
De Martino
Francesca
F
Sprio
Andrea Elio
AE
Daffara
Fulvia
F
Terzolo
Massimo
M
Berruti
Alfredo
A
Di Carlo
Francesco
F
Ghezzo
Franco
F
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008297:Male; D008939:Mitotane / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane