Determination of lodenosine and its major metabolite in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry

Citation
Js. Roth et al., Determination of lodenosine and its major metabolite in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry, J MASS SPEC, 35(11), 2000, pp. 1313-1319
Citations number
23
Categorie Soggetti
Chemistry & Analysis","Spectroscopy /Instrumentation/Analytical Sciences
Journal title
JOURNAL OF MASS SPECTROMETRY
ISSN journal
10765174 → ACNP
Volume
35
Issue
11
Year of publication
2000
Pages
1313 - 1319
Database
ISI
SICI code
1076-5174(200011)35:11<1313:DOLAIM>2.0.ZU;2-#
Abstract
A sensitive and selective method for the determination of 2'-beta -fluoro-2 ',3'-dideoxyadenosine (lodenosine, F-ddA), an experimental anti-AIDS drug, and its major metabolite, 2'-beta -fluoro-2',3'-dideoxyinosine (F-ddI), in human plasma was developed and validated. The procedure employs two interna l standards and a simple ultrafiltration step followed by chromatography on a Betasil C-18 minibore column. An in-line valve is used to remove salts b efore reaching the ion source. Detection is by electrospray ionization tand em mass spectrometry with selected reaction monitoring. The method has a li mit of quantitation of 4 ng ml(-1) (16 nM) for F-ddA and 8 ng ml(-1) (32 nM ) for F-ddI with a linear range up to 2000 ng ml(-1) (7.9 muM) for each. Pr edicted concentrations from a three-day validation study were within 5% of the nominal values for F-ddA and 16% for F-ddI, Intra- and interassay preci sion, as measured by relative standard deviation, was 13% or better for bot h compounds. To achieve good reproducibility, many variables related to the electrospray ionization were optimized for both precision and sensitivity. The method was successfully employed to analyze samples and evaluate plasm a pharmacokinetics from a Phase I clinical trial. Copyright (C) 2000 John W iley & Sons, Ltd.