Abstract
A liquid chromatography-tandem mass spectrometry method is presented that was applied for over five years for routine measurement of the immunosuppressant drugs ciclosporin, everolimus, sirolimus and tacrolimus in blood. The method has been used for analysis of 142 thousand unknowns and has been running 7days a week without a single day shutdown during the entire time. The measuring ranges were 10-1500ng/mL for ciclosporin and 1-50ng/mL for everolimus, sirolimus and tacrolimus. The method validation showed performance meeting the EMA validation guideline requirements and acceptable performance in a proficiency control program. The routine work was based on daily calibrations on two parallel instrument systems, one with multiplexing providing a capacity of 55 injections/h. During week-days up to six batches of samples were run to meet requirements of short reporting times. Although there is still room for method improvements our main conclusion is that the liquid chromatography-tandem mass spectrometry technique provides a viable platform for an analytical routine service for therapeutic drug monitoring of immunosuppressant drugs that meet clinical needs of reporting times and reliable results. We also describe early involvement and education of clinicians to gain acceptance and correct clinical interpretation of analytical results more accurate and precise, but differing from those obtained by immunoassay.