The placental transfer and materno-fetal disposition of methadone in monkeys

A method is described for the quantitation of levo-methadone[3H] in biological samples which involves sample extraction and thin-layer chromatographic separation. Four pregnant Macaca mulata monkeys, two in early gestation and two in late gestation, were given single i.m. injections of levo-methadone[3H]. Twenty-nine fetal and maternal tissues and fluids were assayed to provide quantities of unchanged methadone and methadone plus metabolites. Little placental transfer of methadone or its metabolites occurred during early gestation, but equivalent concentrations of unchanged methadone were found in maternal and fetal tissues during late gestation (maternal brain, 172 ng/g; fetal brain, 123 ng/g). With few exceptions, tissues or fluids from the late gestation mothers showed higher levels of unchanged methadone than those from early gestation mothers at both 1 hour (P less than .001) and 6 hours (P less than .010) after administration. The late gestation mother had a 40.2% greater concentration of unchanged methadone at 6 hours and a 50.1% greater concentration at 1 hour than the early gestation mothers. These data suggest a slowing of metabolism during advanced pregnancy. At 6 hours after administration the eyes of both early and late gestation mothers and late gestation fetuses showed the highest concentrations of unchanged methadone of any maternal or fetal tissue. This localization of methadone appears to be associated with pigmented epithelium.