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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 ShengChang,
Ho IngKang,
Wu ShiowLing,
Liu Shu Chih,
Kuo HsiangWei,
Lin KehMing,
Liu YuLi
Publication year - 2010
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1363
Subject(s) - enantiomer , chemistry , methadone , chromatography , methadone maintenance , measure (data warehouse) , pharmacology , organic chemistry , medicine , database , computer science
Abstract 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 © 2009 John Wiley & Sons, Ltd.