Quantitation of Buprenorphine, Norbuprenorphine, Buprenorphine Glucuronide, Norbuprenorphine Glucuronide, and Naloxone in Urine by LC-MS/MS

  • Stephanie J. MarinEmail author
  • Gwendolyn A. McMillin
Part of the Methods in Molecular Biology book series (MIMB, volume 1383)


Buprenorphine is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Some formulations of buprenorphine also contain naloxone to discourage misuse. The major metabolite of buprenorphine is norbuprenorphine. Both compounds are pharmacologically active and both are extensively metabolized to their glucuronide conjugates, which are also active metabolites. Direct quantitation of the glucuronide conjugates in conjunction with free buprenorphine, norbuprenorphine, and naloxone in urine can distinguish compliance with prescribed therapy from specimen adulteration intended to mimic compliance with prescribed buprenorphine.

This chapter quantitates buprenorphine, norbuprenorphine, their glucuronide conjugates and naloxone directly in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine is pretreated with formic acid and undergoes solid phase extraction (SPE) prior to analysis by LC-MS/MS.

Key words

Buprenorphine LC/MS/MS Urine Suboxone Zubsolv 


  1. 1.
    Heikman P et al (2013) Urine naloxone concentration at different phases of buprenorphine maintenance treatment. Drug Test Anal 6(3):220–225CrossRefPubMedGoogle Scholar
  2. 2.
    Al-Asmari AI, Anderson RA (2008) Comparison of nonhydrolysis and hydrolysis methods for the determination of buprenorphine metabolites in urine by liquid chromatography-tandem mass spectrometry. J Anal Toxicol 32(9):744–753CrossRefPubMedGoogle Scholar
  3. 3.
    McMillin GA et al (2012) Patterns of free (unconjugated) buprenorphine, norbuprenorphine, and their glucuronides in urine using liquid chromatography-tandem mass spectrometry. J Anal Toxicol 36(2):81–87CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.ARUP Institute for Clinical and Experimental PathologySalt Lake CityUSA
  2. 2.ARUP LaboratoriesSalt Lake CityUSA
  3. 3.Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA

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