title: 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 <8.0%, respectively (n=4031). Evaluation of the method against other methods in an external quality control scheme revealed good agreement by linear regression analysis (y=0.924x+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.
authors: Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia. p.taylor1@uq.edu.au
authors: Paul J
authors: PJ
authors: Taylor
authors: Michael E
authors: ME
authors: Franklin
authors: Chun-Hui
authors: CH
authors: Tai
authors: Peter I
authors: PI
authors: Pillans
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood; D016014:Linear Models; D010743:Phospholipids / Q000097:blood; D015203:Reproducibility of Results; D016559:Tacrolimus / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014180:Transplantation
chemical_list: D007166:Immunosuppressive Agents; D010743:Phospholipids; D016559:Tacrolimus