Gadolinium-based contrast agents: A clinically significant analytical interference in inductively coupled plasma mass spectrometry elemental analysis

Abstract

Background Gadolinium-based contrast agents (GBCAs) have been used in magnetic resonance imaging for the past 30 years, where they have significantly improved the effectiveness of imaging studies. However, the increased usage of gadolinium in the medical community has also resulted in unexpected interferences in other laboratory assays. This has been particularly the case in clinical elemental analysis using inductively coupled plasma mass spectrometry (ICP-MS). Methods By conducting ICP-MS interference experiments, we describe how gadolinium interferes with elemental analysis by space charge effect, double charge effect and the creation of polyatomic interferences. Additionally, by reviewing more than a year of reference laboratory data from our laboratory information system, we determined the number of elemental tests cancelled due to gadolinium interference. Results Interference experiments show that gadolinium normally found in GBCAs can interfere with heavy metals, platinum and selenium analysis of biological fluids using ICP-MS. Within one year, our institution’s metals laboratory had to cancel 42 selenium serum tests and 19 heavy metal urine panels due to potential interference caused by gadolinium. Conclusions GBCAs will continue to be utilized in hospitals around the world. However, clinical laboratories should be wary of potential interferences caused by GBCAs. Relevant interferences include space charge effect, double charge interference, and the formation of polyatomic interferences caused by gadolinium. These interferences can negatively affect patient care by resulting in cancelled laboratory tests and causing patients to have blood redrawn and analysed at a later date leading to delays in their diagnosis/treatment.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee

“…Since their clinical approval and introduction in 1988, GBCAs have been administered in 750 million standard doses (Bayer Healthcare, estimated from multiple internal and external sources). Several interferences on laboratory tests have been described, ranging from commonly used laboratory tests [ 12 ] to more specialized laboratory tests [ 18 ]. The probably most clinically relevant interference is the interference of GBCAs on serum calcium measurement by specific colorimetric assays.…”

A simple equation to correct for gadolinium interference on plasma selenium measurement using inductively coupled plasma mass spectrometry

“…Day et al. 17 reported an approximately 15% reduction in signal for gallium, germanium, yttrium and rhodium in the presence of 1000 mg/L gadolinium. This gadolinium level is significantly higher than that typically observed in samples collected post MRI, however.…”

“…For example, Day et al. 17 reported 42 cancelled serum selenium requests within one year at the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Implementation of a correction equation approach to gadolinium interference will significantly reduce the time and cost associated with such recollections and lead to improved patient management.…”

Atomic spectrometry update: review of advances in the analysis of clinical and biological materials, foods and beverages

“…Experimental quantitation of Gd interferences was investigated this year by a series of Gd spiking experiments. 150 In this work, Day et al demonstrated the space charge effect of Gd on internal standard elements Ga, Ge, Rh and Y by analysing urine samples spiked with 1000 ppm Gd. Analysis of spiked samples demonstrated positive interference in Se measurements from Gd at concentrations >10 000 ppm due to the double charge effect of 156 Gd on 78 Se.…”