ISSN:
1052-9306
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
An automated capillary gas chromatography/tandem mass spectrometry (GC/MS/MS) assay for the simultaneous quantitation of tebufelone (TE) and 13C, 18O-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 18O-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.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bms.1200230206
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