QUANTIFICATION OF PYRAZINAMIDE AND ITS METABOLITES IN PLASMA BY IONIC-PAIR HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY - IMPLICATIONS FOR THE SEPARATION MECHANISM

Pyrazinamide, the amide of pyrazinoic acid, is one of the basic therap eutic agents currently used in combination for chemotherapy of tubercu losis. A reversed-phase high-performance liquid chromatography method based on ionic pair chromatography, was developed after solid-phase ex traction of the analytes from plasma with prior addition of internal s tandard. The main metabolites, pyrazinoic acid, 5-hydroxypyrazinoic ac id and 5-hydroxypyrazinamide, were included as well as uric acid and o ther purine derivatives to allow detailed study of the pharmacokinetic s of the drug, especially in patients with impaired kidney function. S ome interesting features of the chromatographic system giving some ins ight in the retention mechanism and of the solid-phase extraction are discussed in detail. (C) 1998 Elsevier Science B.V.