Determination of gadolinium-based MRI contrast agents in biological and environmental samples: A review

Highlights: ► All major methods for the analysis of Gd-based MRI contrast agents are discussed. ► Biological and environmental samples are covered. ► Pharmacokinetics and species transformation can be investigated. ► The figures of merit as limit of detection and analysis time are described. -- Abstract: The development of analytical methods and strategies to determine gadolinium and its complexes in biological and environmental matrices is evaluated in this review. Gadolinium (Gd) chelates are employed as contrast agents for magnetic resonance imaging (MRI) since the 1980s. In general they were considered as safe and well-tolerated, when in 2006, the disease nephrogenic systemic fibrosis (NSF) was connected to the administration of MRI contrast agents based on Gd. Pathogenesis and etiology of NSF are yet unclear and called for the development of several analytical methods to obtain elucidation in this field. Determination of Gd complex stability in vitro and in vivo, as well as the quantification of Gd in body fluids like blood and urine was carried out. Separation of the Gd chelates was achieved with high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). For detection, various methods were employed, including UV–vis absorbance and fluorescence spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and inductively coupled plasma mass spectrometry (ICP-MS). A second challenge for analysts was the discovery of high concentrations of anthropogenic Gd in surface waters draining populated areas. The source could soon be determined to be the increasing administration of Gd complexes during MRI examinations. Identification and quantification of the contrast agents was carried out in various surface and groundwater samples to determine the behavior and fate of the Gd chelates in the environment. The improvement of limits of detection (LOD) and limits of quantification (LOQ) was and still is the goal of past and ongoing projects