Inductively coupled plasma with mass-spectrometry method development and validation for gadolinium in gadolinium-based contrast agents of pharmaceutical formulations

Abstract

Gadolinium-based contrast agent interacts with the human body temporarily and improves the pictures of inside of the body produced by magnetic resonance imaging, computed tomography, X-rays and ultrasound and it also helps to distinguish the normal from abnormal conditions. In this study, the authors developed a simple, rapid, reliable and robust inductively coupled plasma mass-spectrometry method for estimation of gadolinium in gadolinium-based contrast agents to check the drug quality and ensure the patient safety. The samples were digested at 160°C using the microwave digestion system and the gadolinium was extracted in 0.4% (w/w) nitric acid. Interference of deposited gadolinium on sample cone and skimmer cone were investigated and evaluated. The developed method was validated as per ICH Q2 (R1) guideline and USP. The precision was evaluated with six independent assays of gadolinium in each gadolinium-based contrast agent. The test method was found linear (r2 > 0.999) with five different levels covered from 25~200%, and accurate, mean recoveries were 92.5~107.5% at three different levels covered from 50~150%. The robustness was performed by changing the nitric acid concentration (0.4±0.04%, w/w) in diluent system. This method is suitable to quantitatively determine the amount of gadolinium in gadolinium-based contrast agent of drug products in presence of excipients used in formulation and also in drug substance.