Confirmatory analysis of buprenorphine, norbuprenorphine, and glucuronide metabolites in plasma by LCMSMS. Application to umbilical cord plasma from buprenorphine-maintained pregnant women.
An LCMSMS method was developed and fully validated for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) in 0.5mL plasma, fulfilling confirmation criteria with two transitions for each compound with acceptable relative ion intensities. Transitions monitored were 468.3>396.2 and 468.3>414.3 for BUP, 414.3>340.1 and 414.3>326.0 for NBUP, 644.3>468.1 and 644.3>396.3 for BUP-Gluc, and 590.3>414.3 and 590.3>396.2 for NBUP-Gluc. Linearity was 0.1-50ng/mL for BUP and BUP-Gluc, and 0.5-50ng/mL for NBUP and NBUP-Gluc. Intra-day, inter-day, and total assay imprecision (%RSD) were <16.8%, and analytical recoveries were 88.6-108.7%. Extraction efficiencies ranged from 71.1 to 87.1%, and process efficiencies 48.7 to 127.7%. All compounds showed ion enhancement, except BUP-Gluc that demonstrated ion suppression: variation between 10 different blank plasma specimens was <9.1%. In six umbilical cord plasma specimens from opioid-dependent pregnant women receiving 14-24mg/day BUP, NBUP-Gluc was the predominant metabolite (29.8+/-7.6ng/mL), with BUP-Gluc (4.6+/-4.8ng/mL), NBUP (1.5+/-0.8ng/mL) and BUP (0.4+/-0.2ng/mL). Although BUP biomarkers can be quantified in umbilical cord plasma in low ng/mL concentrations, the significance of these data as predictors of neonatal outcomes is currently unknown.
Concheiro
Marta
M
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Biomedical Research Center (BRC), 251 Bayview Boulevard, Suite 200, Room 05A721, Baltimore, MD 21224, USA.
Jones
Hendreé
H
Johnson
Rolley E
RE
Shakleya
Diaa M
DM
Huestis
Marilyn A
MA
D002047:Buprenorphine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D016014:Linear Models; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000097:blood; D009293:Opioid-Related Disorders / Q000097:blood / Q000188:drug therapy; D011247:Pregnancy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D020719:Glucuronides; D009292:Narcotic Antagonists; D002047:Buprenorphine; C043585:norbuprenorphine