Determination of diclofenac residue in swine tissue following intramuscular administration

Abstract

Diclofenac residue (DF) in swine tissue (liver, kidney, muscle, injection site) were examined using the method of High Performance Liquid Chromatography (HPLC) 15h, 72h, and 120h after i.m. administration of an individual therapeutic dose of diclofenacsodium. At 15h after administration, the highest concentration of DF was found in the kidney (0.614 mg/kg), while a concentration about two times lower was found in the liver (0.316 mg/kg). At the injection site, the DF concentratrion was 0.432 mg/kg, while DF remained in a very low concentration (0.052 mg/kg) in the muscle outside the injection site, which was the lowest concentration in comparison with all the other examined tissues. At 72h after administration, DF was present in all examined tissues, but its concentrations were lower than the level that could be determined using the analytic procedure. Traces of the administered medicine disappeared after the waiting period of 120h in all tissues, except for the injection site. The longer presence of the medicine at the injection site could be a consequence of local inflammation, or irritation, that could cause a reduction in pH values of the area around the injection site, thus leading to slower dissolving and a longer presence of the DF at the injection site.

Rezidue diklofenaka (DF) u tkivima svinja (jetra, bubreg, mišić, injekciono mesto) ispitivane su metodom tečne hromatografije (HPLC) i to 15 časova, 72 časa i 120 časova posle i.m. primene pojedinačne terapijske doze diklofenak-natrijuma. Posle 15 časova od primene, najviša koncentracija DF nađena je u bubregu (0.614 mg/kg), dok je oko dva puta niža koncentracija nađena u jetri (0.316 mg/kg). Na injekcionom mestu, koncentracija DF bila je 0.432 mg/kg, dok se u mišiću izvan injekcionog mesta, DF zadržao u veoma niskoj koncentraciji (0.052 mg/kg), najnižoj u odnosu na sva ostala ispitivana tkiva. Posle 72 časa od primene, DF je bio prisutan u svim ispitivanim tkivima, ali su njegove koncentracije bile niže od granice određivanja primenjenim analitičkim postupkom. Tragovi primenjenog leka gube se posle isteka karence (120 h) u svim tkivima, osim na injekcionom mestu. Duže zadržavanje leka na injekcionom mestu može da bude posledica lokalnog zapaljenja, odnosno iritacije koja bi prouzrokovala sniženje pH vrednosti okoline injekcionog mesta i tako prouzrokovala sporije rastvaranje i duže zadržavanje diklofenaka na mestu primene.