Therapeutic drug monitoring of tacrolimus by liquid chromatography-tandem mass spectrometry: is it truly a routine test?

Abstract Therapeutic drug monitoring of tacrolimus by high-performance liquid chromatography–tandem mass spectrometry has become standard practice. We report on the long-term (4.5 years) use of one such method. Whole blood samples (25 μL) were treated with zinc sulphate (100 μL) and acetonitrile containing ascomycin (internal standard, 250 μL). A high-performance liquid chromatography–tandem mass spectrometer operating in positive ion mode with an electrospray interface was used. Chromatography was performed on a TDM C 18 cartridge column (10 mm × 2.1 mm, 10 μm, Waters) using a switch gradient. A total of 4029 batches were analyzed for tacrolimus; this comprised of 81950 analyses of which 61027 were patient samples. Calibration curves (1.0–50 μg/L) were run on 1765 occasions (mean r 2  = 0.999; range r 2  = 0.988–0.999). Inter-batch accuracy and imprecision of the method (2.5, 12.5 and 30.0 μg/L), when in routine use, was 97.6–98.5% and n  = 4031). Evaluation of the method against other methods in an external quality control scheme revealed good agreement by linear regression analysis ( y  = 0.924 x  + 0.196, r 2  = 0.985). The percentage difference between our results and that of all methods revealed a mean bias of −6.3% and a range of −33.3% to 11.1%. During the evaluation period, four batch failures occurred (0.1% failure rate) and greater than 1000 samples per analytical column was achieved. In conclusion, the described method is ideally suited as a routine test for tacrolimus in the clinical setting.