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Development of a method to measure methadone enantiomers and its metabolites without enantiomer standard compounds for the plasma of methadone maintenance patients.

Author(s): Wang SC, Ho IK, Wu SL, Liu SC, Kuo HW, Lin KM, Liu YL

Affiliation(s): Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.

Publication date & source: 2010-07, Biomed Chromatogr., 24(7):782-8.

Publication type: Evaluation Studies; Research Support, Non-U.S. Gov't

A liquid chromatography-photodiode array (LC-PDA) method using a chiral analytical column was developed to determine the plasma levels of enantiomers of methadone and its chiral metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), without the standard compounds of R-form or S-form enantiomers. This method was established by the characteristics of recombinant cytochrome P-450 (CYP) isozymes, where CYP2C19 prefers to metabolize R-methadone and CYP2B6 prefers to metabolize S-methadone. We incubated the racemic methadone standard with either enzyme for 24 h. We identified the retention times of R- and S-methadone to be around 10.72 and 14.46 min, respectively. Furthermore, we determined the retention times of R- and S-EDDP to be approximately 6.76 and 7.72 min, respectively. No interferences were shown through the retention times of morphine, buprenorphine and diazepam. With the high recovery rate of a solid-phase extraction procedure, this method was applied in analyzing plasma concentrations of seven methadone maintenance patients where R- and S-methadone and R- and S-EDDP were 233.4 +/- 154.9 and 185.9 +/- 136.3 ng/mL and 84.4 +/- 99.4 and 37.6 +/- 22.9 ng/mL, respectively. These data suggest that the present method can be applied for routine assay for plasma methadone and EDDP concentrations for patients under treatment. Copyright (c) 2009 John Wiley & Sons, Ltd.

Page last updated: 2010-10-05

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