Tris buffer = tris(hydroxymethyl)aminomethane (Trometamol)
Toxic effects:
(1) global myocardial hypokinesis (markedly reduced left ventricular ejection fraction) which may present as cardiogenic shock
(2) metabolic/toxic encephalopathy with hyperammonemia and lactic acidosis
The toxic effects usually reverse on discontinuation of the 5-FU infusions, but not always.
Toxic degradation products formed from 5-FU:
(1) fluoracetate (FAC)
(2) fluoracetaldehyde (Facet)
(3) fluoromalonic acid semialdehyde (FMASAld)
When 5-FU is suspended in Tris buffer, toxic degradation products are stabilized as oxazolidines (Facet-Tris, FMASAld-Tris), which degrade at physiologic pH to release the active toxins.
When 5-FU is suspended in water at pH 9.2, the toxic products continue to degrade into less toxic metabolites.
Toxic degradation products can be detected using fluorine-19 NMR.
