Determination of lodenosine and its major metabolite in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry.
Determination of lodenosine and its major metabolite in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry.
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液相色谱/电喷雾电离串联质谱法测定人血浆中洛腺苷及其主要代谢物。
DOI：
10.1002/1096-9888(200011)35:11
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Kelley,JA
中科院分区：
文献类型：
--
作者：
Roth,JS;Wang,J;Kelley,JA
A sensitive and selective method for the determination of 2′‐β‐fluoro‐2′,3′‐dideoxyadenosine (lodenosine, F‐ddA), an experimental anti‐AIDS drug, and its major metabolite, 2′‐β‐fluoro‐2′,3′‐dideoxyinosine (F‐ddI), in human plasma was developed and validated. The procedure employs two internal standards and a simple ultrafiltration step followed by chromatography on a Betasil C18minibore column. An in‐line valve is used to remove salts before reaching the ion source. Detection is by electrospray ionization tandem mass spectrometry with selected reaction monitoring. The method has a limit 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 µM) for each. Predicted concentrations from a three‐day validation study were within 5% of the nominal values for F‐ddA and 16% for F‐ddI. Intra‐ and inter‐assay precision, as measured by relative standard deviation, was 13% or better for both 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 plasma pharmacokinetics from a Phase I clinical trial. Copyright © 2000 John Wiley & Sons, Ltd.
