Validation and application of a method for the determination of buprenorphine, norbuprenorphine, and their glucuronide conjugates in human meconium.
A novel liquid chromatography tandem mass spectrometry method for quantification of buprenorphine, norbuprenorphine, and glucuronidated conjugates was developed and validated. Analytes were extracted from meconium using buffer, concentrated by solid-phase extraction and quantified within 13.5 min. In order to determine free and total concentrations, specimens were analyzed with and without enzyme hydrolysis. Calibration was achieved by linear regression with a 1/x weighting factor and deuterated internal standards. All analytes were linear from 20 to 2000 ng/g with a correlation of determination of >0.98. Accuracy was >or=85.7% with intra-assay and interassay imprecision<or=13.9 and 12.4%, respectively. There was no interference from 70 licit and illicit drugs and metabolites. Buffer extraction followed by SPE yielded recoveries of >or=85.0%. There was suppression of ionization by the polar matrix; however, this did not interfere with sensitivity or analyte quantification due to inclusion of deuterated internal standards. Analytes were stable on the autosampler, at room temperature, at 4 degrees C, and when exposed to three freeze/thaw cycles. This sensitive and specific method can be used to monitor in utero buprenorphine exposure and to evaluate correlations, if any, between buprenorphine exposure and neonatal outcomes.
Kacinko
Sherri L
SL
Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Shakleya
Diaa M
DM
Huestis
Marilyn A
MA
D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000627:therapeutic use; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D020719:Glucuronides / Q000032:analysis* / Q000737:chemistry*; D006801:Humans; D007223:Infant; D008470:Meconium / Q000737:chemistry* / Q000378:metabolism; D009035:Mothers / Q000523:psychology; D009293:Opioid-Related Disorders / Q000188:drug therapy; D011247:Pregnancy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D020719:Glucuronides; D002047:Buprenorphine; C043585:norbuprenorphine