Evaluating co-medication and matrix interference inï¬‚uence on ion yields: A key step in therapeutic drug monitoring HPLC-MS/MS assay validationC. Seger, M. Bock, K. Tentschert, A. Griesmacher
Ann Transplant 2008; 13(1): 38-38 :: ID: 880198
Background: A HPLC-MS/MS assay can outperform immunoassays in TDM due to its increased accuracy (no cross-reactivity with target analyte congeners), sensitivity, and precision. Sudden and unpredictable ion yield attenuation, often only known as "ion suppression effect" can be considered as one central analytical problem of using MS/MS as detector in bio-analysis. Since pathological patient specimen compositions or co-medications are major causes for these effects, measures have to be taken to evaluate these interferences prior to transferring an HPLC-MS/MS assay to routine use.
Material/Methods: A fully validated online SPE-HPLC-MS/MS assay setup (MS: API4000QTrap, SPE column: Oasis HLB, HPLC column: XDB-C-18, 1:20 sample dilution, cycle time 3.5 min) designed for fast routine immunosuppressant TDM was used. Post column infusion or drug spiking experiments were performed. A total of 54 drugs as well as icteric, haemolytic, and lipaemic blank matrices have been screened.
Results: Infusion experiments showed only little inï¬‚uence of the spiked drugs on the analyte ion profiles, whereas spiking experiments unveiled strong signal suppression or enhancement in many cases. For cyclosporine A/tacrolimus the internal standards cyclosporine D/ascomycin balanced the effects, whereas some significant changes were observed for sirolimus and everolimus using either 32-desmethoxyrapamycin or ascomycin as co-eluting internal standards. Pathologically altered matrices did not distinctly inï¬‚uence quantitative results
Conclusions: Even if using highly diluted samples and state of the art 2D chromatography, co-medication can cause ion yield attenuation effects in fast routine TDM. Optimal internal standards are needed to balance such effects.
Keywords: immunosuppressant, Cyclosporine, Tacrolimus
20 Jan 2022 : Original articleImpact on Waitlist Outcomes from Changes in the Medical Eligibility of Candidates for Simultaneous Liver-Ki...
Ann Transplant In Press; DOI: 10.12659/AOT.934850
19 Jan 2022 : Original articleCarbohydrate Metabolism Disorders in Relation to Cardiac Allograft Vasculopathy (CAV) Intensification in He...
Ann Transplant In Press; DOI: 10.12659/AOT.933420
18 Jan 2022 : Original articlePLGA+Fe₃O₄+PFP Nanoparticles Drug-Delivery Demonstrates Potential Anti-Tumor Effects on Tumor Cells
Ann Transplant In Press; DOI: 10.12659/AOT.933246
Most Viewed Current Articles
29 Dec 2021 : Original articleEfficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...
Ann Transplant 2021; 26:e933588
22 Dec 2021 : Original articleComparison of Coronary Artery Calcium Scoring with Dobutamine Stress Echo for Detection of Coronary Artery ...
Ann Transplant 2021; 26:e934163
12 Jan 2022 : Original articleRisk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...
Ann Transplant 2022; 27:e934738