QUANTITATIVE-DETERMINATION OF VALPROIC ACID AND 14 METABOLITES IN SERUM AND URINE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

被引:47
作者
FISHER, E [1 ]
WITTFOHT, W [1 ]
NAU, H [1 ]
机构
[1] FREE UNIV BERLIN,INST TOXICOL & EMBRYOPHARMACOL,W-1000 BERLIN 33,GERMANY
关键词
D O I
10.1002/bmc.1130060108
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A method for the determination of the antiepileptic drug valproic acid and 14 of its metabolites in serum and urine by gas chromatography/mass spectrometry with selected ion monitoring of the trimethylsilylated derivatives has been developed. Sample preparation, including hydrolysis of VPA-conjugates and removal of urea in urine is carried out at pH 5.0 and is rapid and simple. The samples are extracted with ethyl acetate and the concentrated extracts are trimethylsilylated. Analysis with adequate separation of metabolites is achieved with a DB 1701 fused silica (Megabore) capillary column. The method exhibits high recovery and reproducibility and is sufficiently sensitive and selective for analysis of small sample volumes. Application of the method for screening patient serum and urine samples for unusual metabolite patterns, with possible predictive value for early detection of liver injury, is presented.
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页码:24 / 29
页数:6
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