Development and validation of an EI-GC-MS method for the determination of methadone and its major metabolites (EDDP and EMDP) in human breast milk

Journal of Analytical Toxicology
Panagiota NikolaouJulia Atta-Politou

Abstract

Methadone is used extensively for the maintenance of opioid-addicted pregnant women. Because methadone and the two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP), are excreted into breast milk, a sensitive and specific gas chromatographic-mass spectrometric method has been developed, optimized, and validated for their quantitative determination in human breast milk. The procedure combined protein precipitation with acetonitrile and solid-phase extraction, using Isolute Confirm HCX mixed-mode SPE columns, with minimal matrix effect. The optimum extraction conditions for all three analytes were evaluated using spiked human breast milk, and the recovery exceeded 93.0%. This assay uses methadone-d(9) as internal standard for the determination of methadone and EMDP, and EDDP-d(3) for the determination of EDDP. Calibration curves were linear within the range of 2.00-1000 microg/L for methadone (R(2) > 0.995) and 1.00-500 microg/L for EDDP (R(2) >0.997) and EMDP (R(2) > 0.991). Intra- and interday accuracy and precision were within the range of 0.8-5.7% and 1.3-5.2%, respectively, for all analytes. The stability study was assessed by fortifying human breast...Continue Reading

Citations

Apr 14, 2010·Analytical and Bioanalytical Chemistry·Bibiana FrígulsSimona Pichini
Mar 29, 2011·Analytical and Bioanalytical Chemistry·M BarrosoM López-Rivadulla
Sep 9, 2011·Bioanalysis·Victoria SamanidouKonstantinos Rentifis
Dec 31, 2015·Journal of Pharmaceutical and Biomedical Analysis·Uwe WolleinNicholas Schramek
Mar 20, 2010·Critical Reviews in Food Science and Nutrition·Elena Rodríguez RodríguezCarlos Díaz Romero
May 9, 2009·Analytical Chemistry·T A BrettellJ R Almirall

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