Determination of dysprosium in monkey serum by inductively-coupled plasma atomic emission spectrometry (ICP-AES) after the administration of Sprodiamide Injection, a new contrast medium for magnetic resonance imaging

Abstract

Sprodiamide Injection (S-043 Injection, Nycomed Salutar; WIN 59080, Sterling Winthrop) is a magnetic susceptibility-based MRI contrast agent which contains 500 mM dysprosium diethylenetriaminepentaacetic acid bis(methylamide) (DyDTPA-BMA), and 25 mM caldiamide sodium (CaNaDTPA-BMA). A study was conducted to evaluate clearance of drug in cynomolgus monkeys. Eighteen cynomolgus monkeys, divided into three groups of six animals each, were administered Sprodiamide Injection intravenously at dose levels of 0.25, 0.5 and 2.5 mmol kg −1 respectively. The concentration of dysprosium in serum was determined in a monkey serum—hydrochloric acid matrix by inductively-coupled plasma atomic emission spectrometry (ICP-AES). The ICP-AES method was demonstrated to be valid for sensitivity, precision, accuracy and specificity. The dynamic range was linear from 0 to 50 μg ml −1 and the limit of quantification was 24 ng ml −1. The measured dysprosium concentration in monkey serum ranged from 0 to 339 μg ml −1 for the 0.25 mmol kg −1 Sprodiamide Injection dose group, from 0 to 633 μg ml −1 for the 0.5 mmol kg −1 and from 0 to 2920 μg ml −1 for 2.5 mmol kg −1 dose groups. Dysprosium was not detected after 480 min in any of the serum samples from the 0.25 and 0.5 mmol kg −1 dose groups after the administration of Sprodiamide Injection. All the monkeys in the 2.5 mmol kg −1 dose group, with one exception, required 720 min for clearance of the drug from the serum. The drug was completely cleared from serum in all monkeys within 24 h.