REVERSED-PHASE LIQUID-CHROMATOGRAPHIC DETERMINATION OF ISONIAZIDE IN HUMAN URINE AS A TEST OF THE GENETICALLY PREDETERMINED TYPE OF BIOTRANSFORMATION BY ACETYLATION

A new method of determination of genetically predetermined type of bio transformation by acetylation rate using reversed-phase liquid chromat ography (RP-HPLC) was described. The method is based on determination of isonicotinic hydrazide (INH) which is excreted with the patient's u rine during 24 h period after oral administration of 0.4 g of the drug . INH is used as pharmacogenetic marker. Precolumn derivatization of 4 -chloro-5,7-dinitrobenzo-furazan is used at RP-HPLC determination of I NH and a new drug phosphabenzide (diphenylphosghinylacetic hydrazide, DPPAH) with specrtophotometric detection in urine. The limit of INH de tection was 0.27 mu g ml(-1) and the one of DPPAH was 0.82 mu g ml(-1) . As a result of pharmacokinetic investigation it was discovered that bimodal distribution by acetylation rate for DPPAH is less apparent th an in the case of INH. It is shown, that immunomodulator xymedone (N-( beta-oxyethyl)-4,6-dimethyldihydropirimidon-2) is the acetylation indu ctor of xenobiotics. (C) 1998 Elsevier Science B.V. All rights reserve d.