Confirmatory analysis of buprenorphine, norbuprenorphine, and glucuronide metabolites in plasma by LCMSMS. Application to umbilical cord plasma from buprenorphine-maintained pregnant women

J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jan 1;878(1):13-20. doi: 10.1016/j.jchromb.2009.11.005.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Buprenorphine / administration & dosage
  • Buprenorphine / analogs & derivatives*
  • Buprenorphine / blood*
  • Chromatography, Liquid / methods*
  • Female
  • Fetal Blood / chemistry*
  • Glucuronides / blood*
  • Humans
  • Linear Models
  • Narcotic Antagonists / administration & dosage
  • Narcotic Antagonists / blood
  • Opioid-Related Disorders / blood
  • Opioid-Related Disorders / drug therapy
  • Pregnancy
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*

Substances

  • Glucuronides
  • Narcotic Antagonists
  • Buprenorphine
  • norbuprenorphine