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   <subfield code="a">Simultaneous Determination of Buprenorphine, Norbuprenorphine and Naloxone in Human Plasma by LC-MS-MS</subfield>
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   <subfield code="c">[Ting-Yi Chiang, Li-Heng Pao, Cheng-Huei Hsiong, Pei-Wei Huang, Kai-Wei Lin, Oliver Hu]</subfield>
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   <subfield code="a">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:2mM 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 0.05ngmL−1 for BUP, 0.1ngmL−1 for NBUP and 0.025ngmL−1 for naloxone, respectively. The standard calibration curves of BUP, NBUP and naloxone were linear over the concentration range of 0.05-20ngmL−1, 0.1-20ngmL−1 and 0.025-20ngmL−1, respectively. The precisions (RSD) and accuracies (RE) of LLOQ and other QC samples were in acceptable range, with RSD&lt;20% and RE±20% for LLOQ and RSD&lt;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.</subfield>
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