Measurement and Pharmacokinetics of Acetylsalicylic Acid by a Novel High Performance Liquid Chromatographic Assay

Abstract

Plasma acetylsalicylic acid and salicylic acid are assayed by a specific, rapid, and sensitive high performance liquid chromatographic procedure. The plasma samples are treated with physostigmine to inhibit esterase activity that otherwise will promote enzymatic hydrolysis of acetylsalicylic acid to salicylic acid. Conditions are chosen such that the total in vitro hydrolysis of acetylsalicylic acid is minimized to less than 5%. Plasma samples are deproteinated with methylcyanide. Acetylsalicylic acid and salicylic acid are separated by elution with a mixture of methanol, acetic acid, and water on a reversed-phase octadecyl silane column and detected by ultraviolet absorption. Quantitation is achieved by measuring absolute peak heights. Recovery and repeatability studies are good. No interference was observed when 50 drugs were also present in the various plasma samples. Concentrations of acetylsalicylic acid and salicylic acid can be obtained within 20 min of receipt of the blood specimens. Pharmacokinetic parameters obtained by this method after a single oral dose of 900 mg soluble, effervescent acetylsalicylic acid in normal healthy subjects suggest that absorption, distribution, and elimination of acetylsalicylic acid are rapidly occurring events.