Non-transferrin bound iron.

Non-transferrin-bound iron (NTBI) is an important biomarker related to the iron loading status of patients with certain diseases. NTBI is a highly toxic form of iron capable of generating free radicals and can lead to oxidative damage of various tissues. It is critical to quantify NTBI in blood to ensure personalised patient chelation management and to prevent high iron concentrations that can lead to toxicity and organ failure. Different analytical methods for the direct quantification of NTBI are described in the literature, but none have been translated for use in clinical laboratories. This review provides a critical discussion on the recent breakthroughs and remaining challenges for the direct quantification of NTBI. Most of the developed methods involve lengthy and complex sample preparation, use of expensive reagents and equipment while lacking the required accuracy and reproducibility. Collectively, these factors have limited the clinical translation of the developed methods, and therefore, the need for a reliable and widely accepted analytical method to quantify NTBI remains. Finally, this review explores the potential of rapid and accurate electrochemical techniques that have been demonstrated for environmental samples but are yet to be applied to detect NTBI in human blood plasma/serum and translation to widespread routine clinical use.