HPLC-determination of some antiinflammatory, weak analgesic and uricosuric drugs in human blood plasma and its application to pharmacokinetics.

Abstract

HPLC-determination of naproxen, indomethacin, ketoprofen, fenoprofen ibuprofen, diclofenac sodium, tolfenamic acid, phenylbutazone, mofebutazone, salicylic acid, acetylsalicylic acid, phenacetin, paracetamol, sulfinpyrazone and probenecid by means of an adjustable, rapid accurate and specific method is described. Plasma samples of 0.2 ml were deproteinised and the drugs extracted simultaneously with pure acetonitrile. Aliquots of 25 mul of this primary extract were directly injected on the column. As elution solvent for drug screening was basically used 55% methanol in 50 mM phosphate buffer at pH 4.0. Optimal separation of some drugs or reasonable elution times for others were obtained by varying the methanol concentration of the elution solvent or possibly its pH. The method used for individual drug determinations is very applicable for therapeutic monitoring purposes as well as for use in pharmacokinetic investigations. As an example, the practical detection limit for naproxen in plasma was about 0.2 microgram ml-1. By concentrating the extract this could be lowered to about 0.04 microgram ml-1. The method was applied in a study of the pharmacokinetics of naproxen in a person, who ingested a single oral dose of 2.5 mg kg-1. Pronounced two-compartment kinetics were found. Vc was 0.038 1 kg-1, Vdss 0.138 1 kg-1, t 1/2 (beta) 21.3 hrs, t 1/2 (alpha) 0.99 hr and t 1/2 (ka) 0.67 hr.