False Immunosuppressant Measurement by LC-MS/MS Method Due to Radiopaque Agents

Although liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is preferred as a reliable method, some molecules in the blood matrix may lead to false positive or false negative results. False positive or negative results show the direction of the deviation rate from the target value.

The aim of this study was to investigate the effect of seven different radiopaque agents on four immunosuppressant drugs.

Every agent coded with RM1 to RM7 was added to control materials containing tacrolimus, everolimus, sirolimus, and cyclosporine A drugs. Measurements were performed using an LC-MS/MS instrument. Bias values were calculated to detect the deviation rates.

All RMs led to false negative results in the tacrolimus and cyclosporine A levels at a rate of -19.77% (95% CI, -27.16 to 12.52) to -44.45% (95% CI, -49.20 to -39.69). The smallest deviations were seen in the everolimus levels with the administration of RM6 (gadodiamide) and in the sirolimus levels with RM1 (gadobutrol) at the rates of 4.04% (95% CI, -11.36 to -3.17) and 2.11% (95% CI, -7.18 to 7.11), respectively. The most affected drug by RM4 (gadopentetate dimeglumine salt) was sirolimus at the rate of 114.01% (95% CI, 97.31 - 130.76). RM5 (gadodiamide) interfered cyclosporine A at the most. The highest deviations were observed with the administration of RM3 (iohexol) in the everolimus and sirolimus levels at the rates of 153.72% (95% CI, 142.44 to 164.78) and 171.41% (95% CI, 157.91 to 184.97), respectively.

Radiopaque agents interfered the measurement of immunosuppressant drugs. Especially, everolimus and sirolimus levels were affected due to using iohexol. The choice of gadodiamide or ioversol is important to reduce the risk of interference for everolimus measurement. The blood samples should be obtained for measurement of drug levels before contrast-enhanced imaging.