ENDOGENOUS PLASMA N-ACETYLCYSTEINE AND SINGLE DOSE ORAL BIOAVAILABILITY FROM 2 DIFFERENT FORMULATIONS AS DETERMINED BY A NEW ANALYTICAL METHOD

A method to quantitate N-acetylcysteine in plasma using reductive cleavage with tributylphosphine and post-HPLC column derivatisation with o-phthalaldehyde is described. Using this method, endogenous average concentrations of 0.08-mu-M were measured in 10 volunteers participating in a crossover study to compare the bioavailability of two different formulations of N-acetylcysteine. The drug was detected in plasma for up to 12 h after administration of a single oral dose (200 mg); the C(max) values were up to 20 times the endogenous levels. The sensitivity and selectivity of the method should thus enable the behaviour of N-acetylcysteine after oral administration to be properly described and bioavailability studies to be performed.