Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 850, Issue 1-2, Pages 538-543Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2006.11.025
Keywords
buprenorphine; norbuprenorphine; (S)-methadone; (R)-methadone; (S)-EDDP; (R)-EDDP; chiral chromatography; AGP chiral stationary phase; LC-MS
Funding
- Intramural NIH HHS Funding Source: Medline
- NIDA NIH HHS [DA00332, R01 DA008045, DA08045, K02 DA000332] Funding Source: Medline
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A previously reported enantioselective LC-MS assay for the determination of (R)- and (S)-methadone [Met] and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine [EDDP] (the primary metabolite of Met) has been adapted for use in the simultaneous determination of the plasma concentrations of Met, EDDP, buprenorphine (Bu) and norbuprenorphine (norBu). All of the target compounds were separated within 15 min using an alpha(1)-acid glycoprotein chiral stationary phase, a mobile phase composed of acetonitrile: ammonium acetate buffer [10 mM, pH 7.0] in a ratio of 18:82 (v/v), a flow rate of 0.9 ml/min at 25 degrees C. Deuterium labeled compounds were used as internal standards [d(4)-Bu, d(3)-norBu, (R,S)-d(3)-Met and (R,S)-d(3)-EDDP] and linear relationships between peak height ratios and drug concentrations were obtained for Bu and norBu in the range 0.2-12 ng/ml with correlation coefficients greater than 0.999. The relative standard deviations (%R.S.D.) for the intra- and inter-day precision of the method were < 4.5% and for accuracy was < 4.0%. The method was validated and used to analyze plasma samples obtained from opioid dependent methadone-maintained adults enrolled in a research study. (c) 2006 Elsevier B.V. All rights reserved.
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