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

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.