Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs
Introduction: Advances in liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) have enabled the quantification of immunosuppressants using microsampling techniques. In this context, dried matrix on paper discs (DMPD) could be a useful alternative to conventional venipuncture. Althoug...
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| Format: | Article |
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Elsevier
2022-08-01
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| Series: | Journal of Mass Spectrometry and Advances in the Clinical Lab |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667145X22000177 |
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| author | Ignacio Guillermo Bressán María Isabel Giménez Susana Francisca Llesuy |
| author_facet | Ignacio Guillermo Bressán María Isabel Giménez Susana Francisca Llesuy |
| author_sort | Ignacio Guillermo Bressán |
| collection | DOAJ |
| description | Introduction: Advances in liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) have enabled the quantification of immunosuppressants using microsampling techniques. In this context, dried matrix on paper discs (DMPD) could be a useful alternative to conventional venipuncture. Although analytical validation is necessary to establish the suitability of method performance, it is not sufficient to proceed with its implementation into routine clinical practice. Also necessary is that equivalence between sampling methods be demonstrated in a clinical validation study. Objetives: To clinically validate a LC-MS/MS method for the quantification of tacrolimus, sirolimus, everolimus and cyclosporin A using DMPD. Methods: According to the recommendations of international guidelines, at least 40 whole blood (WB) and DMPD paired samples for each analyte were collected by skilled technicians and analyzed using LC-MS/MS. Results were evaluated in terms of statistical agreement and bias values at medical decision points. Results: For all analytes, Passing-Bablok regression analysis revealed that confidence intervals (CIs) for slopes and intercepts included 1 and 0, respectively. It also showed that biases at medical decision points were not clinically relevant. No statistically significant differences between DMPD and WB were found using difference plots and agreement analysis. In this regard, CIs for bias estimators included 0, and more than 95% of the results fell within the limits of agreement. Conclusion: The feasibility of the clinical application of simultaneous quantification of tacrolimus, sirolimus, everolimus and cyclosporin A in DMPD was demonstrated. Results showed that this microsampling technique is interchangeable with conventional WB sampling when specimens are collected by trained personnel. |
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| format | Article |
| id | doaj.art-dec05789f52741a5a7e7426085679db0 |
| institution | Directory Open Access Journal |
| issn | 2667-145X |
| language | English |
| last_indexed | 2024-04-14T02:07:29Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Mass Spectrometry and Advances in the Clinical Lab |
| spelling | doaj.art-dec05789f52741a5a7e7426085679db02022-12-22T02:18:37ZengElsevierJournal of Mass Spectrometry and Advances in the Clinical Lab2667-145X2022-08-01251218Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discsIgnacio Guillermo Bressán0María Isabel Giménez1Susana Francisca Llesuy2Laboratory of Mass Spectrometry, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Department of Chemistry, Instituto Universitario Escuela de Medicina del Hospital Italiano, Buenos Aires, Argentina; Corresponding author at: Laboratory of Mass Spectrometry, Hospital Italiano de Buenos Aires, Tte. Juan Domingo Perón 4190 (C1181ACH), Buenos Aires, Argentina.Laboratory of Mass Spectrometry, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Department of Clinical Biochemistry, Instituto Universitario Escuela de Medicina del Hospital Italiano, Buenos Aires, ArgentinaDepartment of Chemistry, Instituto Universitario Escuela de Medicina del Hospital Italiano, Buenos Aires, ArgentinaIntroduction: Advances in liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) have enabled the quantification of immunosuppressants using microsampling techniques. In this context, dried matrix on paper discs (DMPD) could be a useful alternative to conventional venipuncture. Although analytical validation is necessary to establish the suitability of method performance, it is not sufficient to proceed with its implementation into routine clinical practice. Also necessary is that equivalence between sampling methods be demonstrated in a clinical validation study. Objetives: To clinically validate a LC-MS/MS method for the quantification of tacrolimus, sirolimus, everolimus and cyclosporin A using DMPD. Methods: According to the recommendations of international guidelines, at least 40 whole blood (WB) and DMPD paired samples for each analyte were collected by skilled technicians and analyzed using LC-MS/MS. Results were evaluated in terms of statistical agreement and bias values at medical decision points. Results: For all analytes, Passing-Bablok regression analysis revealed that confidence intervals (CIs) for slopes and intercepts included 1 and 0, respectively. It also showed that biases at medical decision points were not clinically relevant. No statistically significant differences between DMPD and WB were found using difference plots and agreement analysis. In this regard, CIs for bias estimators included 0, and more than 95% of the results fell within the limits of agreement. Conclusion: The feasibility of the clinical application of simultaneous quantification of tacrolimus, sirolimus, everolimus and cyclosporin A in DMPD was demonstrated. Results showed that this microsampling technique is interchangeable with conventional WB sampling when specimens are collected by trained personnel.http://www.sciencedirect.com/science/article/pii/S2667145X22000177Dried matrix on paper discs (DMPD)ImmunosuppressantsLiquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)Method comparisonClinical validation |
| spellingShingle | Ignacio Guillermo Bressán María Isabel Giménez Susana Francisca Llesuy Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs Journal of Mass Spectrometry and Advances in the Clinical Lab Dried matrix on paper discs (DMPD) Immunosuppressants Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) Method comparison Clinical validation |
| title | Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs |
| title_full | Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs |
| title_fullStr | Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs |
| title_full_unstemmed | Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs |
| title_short | Clinical validation of a liquid chromatography-tandem mass spectrometry method for the quantification of calcineurin and mTOR inhibitors in dried matrix on paper discs |
| title_sort | clinical validation of a liquid chromatography tandem mass spectrometry method for the quantification of calcineurin and mtor inhibitors in dried matrix on paper discs |
| topic | Dried matrix on paper discs (DMPD) Immunosuppressants Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) Method comparison Clinical validation |
| url | http://www.sciencedirect.com/science/article/pii/S2667145X22000177 |
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