Quantitative Determination of Forphenicinol and Its Metabolites in Human Serum and Urine by Gas Chromatography : Mass Spectrometry with Selected Ion Monitoring

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A simple and sensitive method for the determination of forphenicinol (L-(3-hydroxy-4-hydroxymethylphenyl)glycine) and its metabolites (M-1-M-5) in human serum and urine has been developed by means of gas chromatography-mass spectrometry with selected ion monitoring.Forphenicinol (FPL) and M-2 (3-hydroxy-4-hydroxymethylbenzylamine) were quantified at the same time as the trimethylsilyl (TMS) derivatives. M-1 (α-(3-hydroxy-4-hydroxymethylphenyl)-α-oxoacetic acid) was methoximated, and then analyzed simultaneously with M-3 (3-hydroxy-4-hydroxymethylbenzoic acid) and M-4 (hydroxyterephthalic acid) after trimethylsilylation. On the other hand, M-5 (L-N-acetyl(3-hydroxy-4-hydroxymethylphenyl)glycine) was hydrolyzed enzymatically with acylase to convert it into FPL and determined as the TMS derivative.In serum, the calibration range for FPL was 0.02-5 μg/ml. As for urine, the calibration curves were linear in the ranges of 0.04-10 μg/ml for FPL, 0.1-10 μg/ml for M-1,M-3,M-4,and M-5,and 0.4-100 μg/ml for M-2.The metabolic fate of FPL in man was investigated after a single oral dose (50 mg) of FPL to each of five healthy volunteers. In the serum, unchanged FPL was found but no metabolites were detected. The serum FPL levels were followed and analyzed pharmacokinetically. In the urine, unchanged FPL and its five metabolites (M-1-M-5) were detected and quantified; M-2 and M-5 were the major urinary metabolites.
公益社団法人日本薬学会の論文
1986-08-25

Quantitative Determination of Forphenicinol and Its Metabolites in Human Serum and Urine by Gas Chromatography : Mass Spectrometry with Selected Ion Monitoring

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