GAS-CHROMATOGRAPHIC TANDEM MASS-SPECTROMETRIC DETERMINATION OF ACETYLSALICYLIC-ACID IN HUMAN PLASMA AFTER ORAL-ADMINISTRATION OF LOW-DOSE ASPIRIN AND GUAIMESAL

A fully validated gas chromatographic-tandem mass spectrometric (GC-MS -MS) method is described for the accurate determination of acetylsalic ylic acid (ASA) in human plasma after a single low-dose oral administr ation of aspirin or guaimesal, an ASA releasing prodrug. ASA and the n ewly prepared O-[H-2(3)]-acetylsalicylic acid (d3-ASA) used as interna l standard were determined in 100-mu l aliquots of plasma by extractiv e pentafluorobenzyl (PFB) esterification using PFB bromide and tetrabu tylammoniumhydrogen sulphate as the esterifying and ion-pairing agent, respectively, and by GC-MS-MS analysis in the negative-ion chemical i onization mode. The overall relative standard deviations were below 8% for ASA levels in the range 0-1 mu g/ml plasma. Mean accuracy was 3.8 % for ASA levels within the range 0-100 ng/ml. The limit of quantitati on of the method was determined as 200 pg/ml ASA at an accuracy of 5.5 % and a precision of 15.2%. The limit of detection was determined as 5 46 amol of ASA at a signal-to-noise ratio of 10:1. (C) 1998 Elsevier S cience B.V.