Simultaneous gas chromatographic-mass spectrophotometric determination of alpha-fluoro-beta-alanine and 5-fluorouracil in plasma.
A gas chromatographic-mass spectrometric (GC-MS) method is reported for simultaneous determination of alpha-fluoro-beta-alanine (FBA), the major end metabolite of 5-fluorouracil (5-FU), and 5-FU in plasma samples isolated from cancer patients. 5-Chlorouracil (5-CIU, 1 micrograms/ml) is added to samples as an internal standard. The method relies on protein precipitation of the plasma sample followed by derivatisation with pentafluorobenzyl bromide. Following sample purification with Sep-pak C18 columns the derivatives are analysed by GC-MS, with FBA, 5-FU and 5-CIU being determined at 36.96-37.03, 46.91-46.98 and 51.99-52.13 min, respectively. The ions measured in each case had m/z of 390, 490 and 506, respectively. The method showed good reproducibility with coefficients of variation between 3 and 10%, with a detection limit of < 1 ng/ml for 5-FU and < 5 ng FBA/ml plasma. The possibility of sensitive determination of FBA without the use of radioisotopes should permit routine estimation of rates of 5-FU metabolism in individual patients.
Anderson
D
D
CRC Institute for Cancer Studies, School of Medicine, University of Birmingham, UK.
Kerr
D J
DJ
Blesing
C
C
Seymour
L W
LW
D000964:Antimetabolites, Antineoplastic / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000737:chemistry; D005464:Fluorobenzenes / Q000737:chemistry; D005472:Fluorouracil / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D016014:Linear Models; D009994:Osmolar Concentration; D015203:Reproducibility of Results; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D005466:Fluorocarbons
D000964:Antimetabolites, Antineoplastic; D001798:Blood Proteins; D005464:Fluorobenzenes; D005472:Fluorouracil; D015091:beta-Alanine; C025063:pentafluorobenzyl bromide; D005466:Fluorocarbons; C032348:alpha-fluoro-beta-alanine