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A Robust Procedure for Determination of Immunosuppressants Cyclosporine A and Tacrolimus in Blood Samples with Detection of LC–MS/MS

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Abstract

The immunosuppressants monitoring is crucial in the treatment of transplant patients to avoid the risk of organ rejection. So it is vital to develop an accurate method to obtain precise and reliable results. Herein, a liquid chromatography tandem mass spectrometry (LC–MS/MS) based method was developed and validated, which could simultaneously realize the accurate quantification of cyclosporine A and tacrolimus with a total run time of 4.5 min. Unlike the previously described methods, the highlight of this assay is that there is no using zinc sulfate in the protein precipitation of the whole blood sample, which can effectively prolong the lifespan of mass spectrometry. In addition, the linearity, matrix effect, carryover, accuracy, intraday and interday precision of this method were investigated. The linear range of tacrolimus and cyclosporine were 1–40 ng/mL and 50–2000 ng/mL, respectively; The correlation coefficients (R2) were both greater than 0.995. The intraday and interday precision of cyclosporine and tacrolimus were ≤ 10%. The lower limit of quantitation (LLOQ) of tacrolimus and cyclosporine A were 1 ng/mL and 50 ng/mL, respectively. The main features of this method are good accuracy, sensitivity, specificity, rapidness, robustness and high throughput. It is suitable for therapeutic drug monitoring of cyclosporine A and tacrolimus in routine clinical diagnostics.

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Acknowledgements

The authors appreciate the financial support of Project Clinical Immunosuppressant program. The authors want to acknowledge the technical and human support provided by adicon clinical laboratory and Department of Chemistry, Northeastern University.

Funding

This work was supported by Clinical mass spectrometry R&D.

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YH: wrote the main manuscript text and all authors reviewed the manuscript.

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Correspondence to Yumei Huo.

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Huo, Y., Zhang, S., Pan, C. et al. A Robust Procedure for Determination of Immunosuppressants Cyclosporine A and Tacrolimus in Blood Samples with Detection of LC–MS/MS. Chromatographia 86, 255–263 (2023). https://doi.org/10.1007/s10337-023-04241-8

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