Simultaneous determination of buprenorphine, norbuprenorphine and naloxone in human plasma by LC-MS-MS

Ting Yi Chiang, Li Heng Pao, Cheng Huei Hsiong, Pei Wei Huang, Kai Wei Lin, Oliver Yoa Pu Hu

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


A novel sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS-MS) method simultaneously determined buprenorphine (BUP) and its active metabolite, norbuprenorphine (NBUP), and a coformulant, naloxone was developed, validated and applied successfully in humans. Buprenorphine-d 4 and norbuprenorphine-d 3 were used as the internal standard. The analysis was performed on a silica column, and the mobile phase was isocratic and composed of acetonitrile:2 mM ammonium formate in H2O (82:18, v/v). Mass spectrometry employed multiple reaction monitoring modes with transitions of m/z 468.1-55.2 for BUP, 414.2-101.2 for NBUP, 328.3-310.3 for naloxone, 472.1-59.2 for buprenorphine-d 4 and 417.2-101.2 for norbuprenorphine-d 3. Lower limit of quantification (LLOQ) of the analytical method was 0.05 ng mL-1 for BUP, 0.1 ng mL-1 for NBUP and 0.025 ng mL-1 for naloxone, respectively. The standard calibration curves of BUP, NBUP and naloxone were linear over the concentration range of 0.05-20 ng mL-1, 0.1-20 ng mL-1 and 0.025-20 ng mL-1, respectively. The precisions (RSD) and accuracies (RE) of LLOQ and other QC samples were in acceptable range, with RSD < 20% and RE ± 20% for LLOQ and RSD < 15% and RE within ±15% for QC samples. The method was accurate, precise and specific, and was applied to the pharmacokinetic study of buprenorphine in healthy volunteers.

Original languageEnglish
Pages (from-to)575-583
Number of pages9
Issue number7-8
Publication statusPublished - Oct 1 2011
Externally publishedYes


  • Buprenorphine
  • LC-MS-MS
  • Naloxone
  • Norbuprenorphine
  • Pharmacokinetics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry


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