The quantitative determination of Gd-DTPA in biological samples by inductively coupled plasma (ICP) spectrometry.

Abstract

To study pharmacokinetics of magnetic resonance contrast agent, Gd-DTPA (Gadolinium-complex of diethylenetriaminepentaacetic acid), the method to determine the concentration of Gd-DTPA was established by using ICP (inductively-coupled plasma) emission spectrometry. The emission intensity in creased linearly against the concentration of Gd-DTPA of more than 0.5 nmol/ml. There was no difference in the emission intensity between Gd-DTPA and GdCl3. For extraction of Gd-DTPA, tissue samples were digested at 150°C-180°C with HNO3. About 0.1 g samples of dried tissues were optimal for digestion. Recovery of Gd-DTPA added to control liver was more than 90 % with excellent reproducibility, but at concentrations below 5 nmol the reproducibility was getting worse. From these findings, the detection limit was found to be 10 nmol/g wet tissue. Gd was not detected in any tissues of control rat. The recovery of Gd-DTPA added to plasma was compared among three pretreatment methods (1. dilution method 2. digestion with HNO3 3. deproteinization by perchloric acid). The deproteinization method was the most appropriate in respect to the recovery and the operation. The detection limit in plasma was 2.5 nmol/ml. In the tissues of rat, given Gd-14C-DTPA, the amount of Gd-DTPA measured by this assay method was almost consistent with that obtained by the radioactivity measurement. Gd-DTPA in the tissues and the plasma of rat after intraveneous administration (2.5 mmol/kg) was determined by ICP analysis. Gd-DTPA rapidly disappeared from plasma within 6 hrs. In the liver, spleen and bone, Gd-DTPA almost completely disappeared within 14 days, but in the kidneys, 60 days were required for complete elimination. In conclusion, ICP spectrometry can be adapted to pharmacokinetic study of Gd-DTPA.