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Automated gas chromatography/tandem mass spectrometry assay for tebufelone and a 13 C, 18 O‐labeled analog in plasma: Applicability to absolute bioavailability determination
Author(s) -
Dobson R. L. M.,
Kelm G. R.,
Neal D. M.
Publication year - 1994
Publication title -
biological mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1052-9306
DOI - 10.1002/bms.1200230206
Subject(s) - chemistry , chromatography , mass spectrometry , bioavailability , analytical chemistry (journal) , gas chromatography/tandem mass spectrometry , gas chromatography , tandem mass spectrometry , pharmacokinetics , stable isotope ratio , bioinformatics , biology , medicine , physics , quantum mechanics
An automated capillary gas chromatography/tandem mass spectrometry (GC/MS/MS) assay for the simultaneous quantitation of tebufelone (TE) and 13 C, 18 O‐labeled TE (TE‐CO) in plasma was developed. This method permits the use of stable isotope coadministration (TE and TE‐CO dosed concurrently via peroral and intravenous routes, respectively) for the determination of TE absolute bioavailability. The selectivity of MS/MS conducted on a triple‐quadrupole instrument allowed minimal sample preparation and rapid analysis. Electron ionization produced molecular ions (M +. ) for TE, TE‐CO, and the 3‐methyl‐TE internal standard, which were selected in Q1 to undergo collisionally activated dissociation in Q2. Quantitation was achieved through monitoring product ions at m/z 248, 251, and 248, respectively, in Q3. A 2‐1000 ng per sample (40 pg to 20 ng injected) quantitation range provided access to an effective 1–5000 p.p.b. plasma concentration range (0.2–2 g samples) for both TE and TE‐CO. The assay showed no bias and less than 8% relative standard deviation over the entire range. The method was used to determine plasma levels of TE and TE‐CO in four dogs receiving 2.5:2.5 mg/kg TE:TE‐CO, intravenously. The pharmacokinetics of both isotopomers proved to be identical, indicating no isotope effect and verifying the chemical stability of the 18 O‐carbonyl label under these dosing conditions. In addition, the applicability of this analytical approach to the determination of TE peroral bioavailability was initially tested in dogs.