TY - JOUR
T1 - Simultaneous determination of buprenorphine, norbuprenorphine and the enantiomers of methadone and its metabolite (EDDP) in human plasma by liquid chromatography/mass spectrometry
AU - Rodriguez-Rosas, Maria Esther
AU - Lofwall, Michelle R.
AU - Strain, Eric C.
AU - Siluk, Danuta
AU - Wainer, Irving W.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the NIH, National Institute on Aging and grants DA08045 and DA00332 from the National Institute on Drug Abuse. M.E.R.R. gratefully thanks Dr. J.T. Lee from Advanced Separation Technologies, Inc. and Mr. Philip Kim from Waters Corporation for their helpful suggestions and technical expertise.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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 α1-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 °C. Deuterium labeled compounds were used as internal standards [d4-Bu, d3-norBu, (R,S)-d3-Met and (R,S)-d3-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.
AB - 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 α1-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 °C. Deuterium labeled compounds were used as internal standards [d4-Bu, d3-norBu, (R,S)-d3-Met and (R,S)-d3-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.
KW - (R)-EDDP
KW - (R)-methadone
KW - (S)-EDDP
KW - (S)-methadone
KW - AGP chiral stationary phase
KW - Buprenorphine
KW - Chiral chromatography
KW - LC-MS
KW - Norbuprenorphine
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U2 - 10.1016/j.jchromb.2006.11.025
DO - 10.1016/j.jchromb.2006.11.025
M3 - Article
C2 - 17141582
AN - SCOPUS:34247260510
SN - 1570-0232
VL - 850
SP - 538
EP - 543
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
IS - 1-2
ER -