Therapeutic monitoring of immunosuppressants is a key tool in the treatment of transplant patients. It is essential to develop accurate methods to obtain precise and reliable results. a simple protein precipitation method with absence of zinc sulfate was explored to pretreat blood samples, the influence of matrix was eliminated, Cyclosporine A and Tacrolimus were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The linearity, matrix effect, carry over, accuracy, intraday and interday precision of this method were investigated. The linear relationship of tacrolimus and cyclosporine were 1–40 ng/mL and 50-2000 ng/mL, respectively; The correlation coefficient (R2) was 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− 1 and 50 ng mL− 1, respectively. The main features of this method are simplicity, promptness, robustness, high sensitivity and throughput and good selectivity. It is suitable for therapeutic drug monitoring of cyclosporine A and tacrolimus in routine clinical diagnostics.
