Simultaneous determination of three iodinated contrast media in human plasma by LC/MS-MS and its clinical application

Iodinated contrast media (ICM), including iohexol, iopromide and iodixanol, have significantly enhanced diagnostic accuracy, particularly in cardiovascular and cerebrovascular diseases. The three ICM is tailored to specific patient needs and diagnostic contexts. However, excessive doses of ICM may induce adverse reactions, including nephrotoxicity. Accurate measurement of ICM concentration is essential for reducing renal burden and ensuring patient safety. Current methods for quantifying ICM are often limited to single-analyte detection (especially iohexol), which is inefficient for clinical practice. Therefore, this method aims to develop and validate a rapid, generic LC-MS/MS method for simultaneously quantifying iohexol, iopromide, and iodixanol in human plasma to improve patient management and prognosis. An LC-MS/MS-based approach was established utilizing an C18 column coupled with a Xevo TQ-S triple quadrupole mass spectrometer. Sample preparation involved protein precipitation, while chromatographic separation was achieved using acetonitrile and 0.1 % formic acid in water. The developed LC-MS/MS method achieved satisfactory separation of the three ICM within 1.5 min. Calibration curves for iohexol, iopromide, and iodixanol showed good linearity in 5.00-5000, 5.00-5000 and 10.0 ∼ 10000 µg/mL, respectively. The method was effectively applied to analyze 71 plasma samples from 9 patients, highlighting its clinical utility. A rapid and generic LC-MS/MS method streamlines sample preparation and standardizes laboratory workflows, making it suitable for clinical bio-samples.