Determination of acetylsalicylic acid and its major metabolite, salicylic acid, in human plasma using liquid chromatography–tandem mass spectrometry: application to pharmacokinetic study of Astrix^® in Korean healthy volunteers

Abstract

The first liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of acetylsalicylic acid (aspirin, ASA) and one of its major metabolites, salicylic acid (SA), in human plasma using simvastatin as an internal standard has been developed and validated. For ASA analysis, a plasma sample containing potassium fluoride was extracted using a mixture of ethyl acetate and diethyl ether in the presence of 0.5% formic acid. SA, a major metabolite of ASA, was extracted from plasma using protein precipitation with acetonitrile. The compounds were separated on a reversed-phase column with an isocratic mobile phase consisting of acetonitrile and water containing 0.1% formic acid (8:2, v/v). The ion transitions recorded in multiple reaction monitoring mode were m/z 179 --> 137, 137 --> 93 and 435 --> 319 for ASA, SA and IS, respectively. The coefficient of variation of the assay precision was less than 9.3%, and the accuracy exceeded 86.5%. The lower limits of quantification for ASA and SA were 5 and 50 ng/mL, respectively. The developed assay method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after single oral administration of Astrix (entero-coated pellet, 100 mg of aspirin) to 10 Korean healthy male volunteers.

Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

“…3A). Similarly, at concentrations of aspirin and celecoxib achieved in plasma with typical dosages of these drugs (26,27), celecoxib largely prevented aspirin inhibition (Fig. 3B).…”

Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

“…However, published pharmacokinetics studies on this aspirin dose have revealed contradictory C max depending on formulation, such as soluble, rapid-release, or chewable 100 mg tablets exhibiting minor differences [22,23,33]; by contrast, the enteric or controlled release tablets showed wide and significant variations [37,38]. Our in vitro results simulated human plasma levels based on 100 mg rapid-acting aspirin formulations (soluble and rapid-release tablets), whose quick action is desirable during the acute onset of symptoms, such as in MI.…”

Comparative Bioavailability Study of Two 81 mg Coated Tablet Formulations of Acetylsalicylic Acid in Fasting Healthy Volunteers

“…The AUC 0-∞ values were 23800 and 21527 ng.h/mL and the t 1/2 was 3.17 and 2.65 h for the test and for the reference formulation, respectively. Bae et al [2] reported values of 3780 ng/mL for C max , 4.45 h for t max , 18200 ng.h/mL for AUC 0-∞ and 2.04 for t 1/2 after a single oral dose administration of an enteric-coated pellets 100 mg acetylsalicylic acid in healthy volunteers.…”

“…Moreover, in low-dose it is also used as antithrombotic agent to inhibit cyclooxygenase-dependent platelet aggregation responsible for the formation of thrombi, which may be related to myocardial infarction and stroke [1][2][3].…”

“…The maximum plasma concentration (C max ) was 170 ng/mL reached in 3.25 (t max ) for acetylsalicylic acid and 3780 ng/mL with t max of 4.75 h for salicylic acid. Their elimination half-life (t1/2) was 0.65 and 2.04 h for acetylsalicylic acid and salicylic acid, respectively, after a single oral dose administration of an enteric-coated pellets 100 mg acetylsalicylic acid in healthy volunteers [2].…”