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J Anal Toxicol. 1997 Oct;21(6):406-14.

Determination of buprenorphine in human plasma by gas chromatography-positive ion chemical ionization mass spectrometry and liquid chromatography-tandem mass spectrometry.

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  • 1Center for Human Toxicology, University of Utah, Salt Lake City 84112, USA.


Buprenorphine is used for the management of pain and has been advocated for the treatment of opioid addiction. Therapeutic doses result in low plasma concentrations of buprenorphine. In order to assess the safety and efficacy of buprenorphine, sensitive analytical methods are needed. Until recently, gas chromatography-positive ion chemical ionization mass spectrometry (GC-PCI-MS) offered the most sensitive method to selectively quantitate buprenorphine. We have developed and validated a sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) method for buprenorphine. The method is described and compared with a GC-PCI-MS method validated in this laboratory. One-milliliter aliquots of plasma are required for the LC-ESI-MS-MS method and 2-mL aliquots for the GC-PCI-MS method. Buprenorphine-d4 is used as internal standard for both methods. Derivatization with pentafluoropropionic acid anhydride is used for the GC-PCI-MS method, in which the derivatized protonated molecular ions after loss of water are monitored at m/z 596 and 600. For LC-ESI-MS-MS, the parent protonated molecule ions are monitored at m/z 468 and 472. A single-step extraction of basic plasma with n-butyl chloride provided recoveries of 70-87%. Although a limit of quantitation (LOQ) of 0.1 ng/mL could be established for LC-ESI-MS-MS, we could only achieve an LOQ of 0.5 ng/mL with the GC-PCI-MS assay. The GC-PCI-MS method has a linear range of 0.5 to 40 ng/mL (mean r2 = 0.998, n = 7). For quality control samples at 1.0, 2.5, and 12.5 ng/mL, the intra- and interassay coefficients of variation (CV) did not exceed 14%, and percent of targets were within 16%. The LC-ESI-MS-MS method had a linear range of 0.1 to 10 ng/mL (mean r2 = 0.999, n = 7). For quality control samples at 0.25, 2.5 and 7.5 ng/mL, the intra- and interassay CVs did not exceed 4%, and percent of targets were within 12%. Stability studies demonstrated buprenorphine was stable for up to 24 h, 125 days, and 55 days when stored at room temperature, 4 degrees C, and -20 degrees C, respectively. The utility of the lower LOQ was demonstrated in 40 plasma samples collected up to 96 h after a sublingual dose of buprenorphine; 10 were quantitatable using GC-PCI-MS and 38 using LC-ESI-MS-MS.

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