Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface
- Autores
- Nazdrajic, Emir; Tascon, Marcos; Rickert, Daniel A.; Gómez Ríos, German A.; Kulasingam, Vathany; Pawliszyn, Janusz B.
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Immunosuppressive drugs are administered to decrease immune system activity (e.g. of patients undergoing solid organ transplant). Concentrations of immunosuppressive drugs (ISDs) in circulating blood must be closely monitored during the period of immunosuppression therapy due to adverse effects that take place when concentration levels fall outside of the very narrow therapeutic concentration range of these drugs. This study presents the rapid determination of four relevant immunosuppressive drugs (tacrolimus, sirolimus, everolimus, and cyclosporine A) in whole human blood by directly coupling solid-phase microextraction to mass spectrometry via the microfluidic open interface (Bio-SPME-MOI-MS/MS). The BioSPME-MOI-MS/MS method offers ≤ 10% imprecision of in-house prepared quality controls over a 10-day period, ≤ 10% imprecision of ClinCal® Recipe calibrators over a three-day period, and single total turnaround time of ∼ 60 min (4.5 min for high throughput). The limits of quantification were determined to be 0.8 ng mL−1 for tacrolimus, 0.7 ng mL−1 sirolimus, 1.0 ng mL−1 for everolimus, and 0.8 ng mL−1 for cyclosporine. The limits of detection were determined to be 0.3 ng mL−1 for tacrolimus, 0.2 ng mL−1 for sirolimus, 0.3 ng mL−1 for everolimus, and 0.3 ng mL−1 for cyclosporine A. The R2 values for all analytes were above 0.9992 with linear dynamic range from 1.0 mL−1 to 50.0 ng mL−1 for tacrolimus, sirolimus, and everolimus while from 2.5 ng mL−1 to 500.0 ng mL−1 for cyclosporine A. To further evaluate the performance of the present method, 95 residual whole blood samples of tacrolimus and sirolimus from patients undergoing immunosuppression therapy were used to compare the Bio-SPME-MOI-MS/MS method against a clinically validated reference method based on chemiluminescent microparticle immunoassay, showing acceptable results. Our results demonstrated that Bio-SPME-MOI-MS/MS can be considered as a suitable alternative to existing methods for the determination of immunosuppressive drugs in whole blood providing faster analysis, better selectivity and sensitivity, and a wider dynamic range than current existing approaches.
Fil: Nazdrajic, Emir. University of Waterloo; Canadá
Fil: Tascon, Marcos. University of Waterloo; Canadá. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; Argentina
Fil: Rickert, Daniel A.. University of Waterloo; Canadá
Fil: Gómez Ríos, German A.. University of Waterloo; Canadá
Fil: Kulasingam, Vathany. University of Toronto; Canadá. University of Toronto; Canadá
Fil: Pawliszyn, Janusz B.. University of Waterloo; Canadá - Materia
-
CYCLOSPORINE
EVEROLIMUS
MASS SPECTROMETRY
MICROFLUIDIC OPEN INTERFACE
SIROLIMUS
SOLID-PHASE MICROEXTRACTION
TACROLIMUS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/160845
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Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interfaceNazdrajic, EmirTascon, MarcosRickert, Daniel A.Gómez Ríos, German A.Kulasingam, VathanyPawliszyn, Janusz B.CYCLOSPORINEEVEROLIMUSMASS SPECTROMETRYMICROFLUIDIC OPEN INTERFACESIROLIMUSSOLID-PHASE MICROEXTRACTIONTACROLIMUShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Immunosuppressive drugs are administered to decrease immune system activity (e.g. of patients undergoing solid organ transplant). Concentrations of immunosuppressive drugs (ISDs) in circulating blood must be closely monitored during the period of immunosuppression therapy due to adverse effects that take place when concentration levels fall outside of the very narrow therapeutic concentration range of these drugs. This study presents the rapid determination of four relevant immunosuppressive drugs (tacrolimus, sirolimus, everolimus, and cyclosporine A) in whole human blood by directly coupling solid-phase microextraction to mass spectrometry via the microfluidic open interface (Bio-SPME-MOI-MS/MS). The BioSPME-MOI-MS/MS method offers ≤ 10% imprecision of in-house prepared quality controls over a 10-day period, ≤ 10% imprecision of ClinCal® Recipe calibrators over a three-day period, and single total turnaround time of ∼ 60 min (4.5 min for high throughput). The limits of quantification were determined to be 0.8 ng mL−1 for tacrolimus, 0.7 ng mL−1 sirolimus, 1.0 ng mL−1 for everolimus, and 0.8 ng mL−1 for cyclosporine. The limits of detection were determined to be 0.3 ng mL−1 for tacrolimus, 0.2 ng mL−1 for sirolimus, 0.3 ng mL−1 for everolimus, and 0.3 ng mL−1 for cyclosporine A. The R2 values for all analytes were above 0.9992 with linear dynamic range from 1.0 mL−1 to 50.0 ng mL−1 for tacrolimus, sirolimus, and everolimus while from 2.5 ng mL−1 to 500.0 ng mL−1 for cyclosporine A. To further evaluate the performance of the present method, 95 residual whole blood samples of tacrolimus and sirolimus from patients undergoing immunosuppression therapy were used to compare the Bio-SPME-MOI-MS/MS method against a clinically validated reference method based on chemiluminescent microparticle immunoassay, showing acceptable results. Our results demonstrated that Bio-SPME-MOI-MS/MS can be considered as a suitable alternative to existing methods for the determination of immunosuppressive drugs in whole blood providing faster analysis, better selectivity and sensitivity, and a wider dynamic range than current existing approaches.Fil: Nazdrajic, Emir. University of Waterloo; CanadáFil: Tascon, Marcos. University of Waterloo; Canadá. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; ArgentinaFil: Rickert, Daniel A.. University of Waterloo; CanadáFil: Gómez Ríos, German A.. University of Waterloo; CanadáFil: Kulasingam, Vathany. University of Toronto; Canadá. University of Toronto; CanadáFil: Pawliszyn, Janusz B.. University of Waterloo; CanadáElsevier Science2021-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/160845Nazdrajic, Emir; Tascon, Marcos; Rickert, Daniel A.; Gómez Ríos, German A.; Kulasingam, Vathany; et al.; Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface; Elsevier Science; Analytica Chimica Acta; 1144; 2-2021; 53-600003-2670CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.aca.2020.11.056info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0003267020311867info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:18:21Zoai:ri.conicet.gov.ar:11336/160845instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:18:21.613CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface |
title |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface |
spellingShingle |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface Nazdrajic, Emir CYCLOSPORINE EVEROLIMUS MASS SPECTROMETRY MICROFLUIDIC OPEN INTERFACE SIROLIMUS SOLID-PHASE MICROEXTRACTION TACROLIMUS |
title_short |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface |
title_full |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface |
title_fullStr |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface |
title_full_unstemmed |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface |
title_sort |
Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface |
dc.creator.none.fl_str_mv |
Nazdrajic, Emir Tascon, Marcos Rickert, Daniel A. Gómez Ríos, German A. Kulasingam, Vathany Pawliszyn, Janusz B. |
author |
Nazdrajic, Emir |
author_facet |
Nazdrajic, Emir Tascon, Marcos Rickert, Daniel A. Gómez Ríos, German A. Kulasingam, Vathany Pawliszyn, Janusz B. |
author_role |
author |
author2 |
Tascon, Marcos Rickert, Daniel A. Gómez Ríos, German A. Kulasingam, Vathany Pawliszyn, Janusz B. |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
CYCLOSPORINE EVEROLIMUS MASS SPECTROMETRY MICROFLUIDIC OPEN INTERFACE SIROLIMUS SOLID-PHASE MICROEXTRACTION TACROLIMUS |
topic |
CYCLOSPORINE EVEROLIMUS MASS SPECTROMETRY MICROFLUIDIC OPEN INTERFACE SIROLIMUS SOLID-PHASE MICROEXTRACTION TACROLIMUS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Immunosuppressive drugs are administered to decrease immune system activity (e.g. of patients undergoing solid organ transplant). Concentrations of immunosuppressive drugs (ISDs) in circulating blood must be closely monitored during the period of immunosuppression therapy due to adverse effects that take place when concentration levels fall outside of the very narrow therapeutic concentration range of these drugs. This study presents the rapid determination of four relevant immunosuppressive drugs (tacrolimus, sirolimus, everolimus, and cyclosporine A) in whole human blood by directly coupling solid-phase microextraction to mass spectrometry via the microfluidic open interface (Bio-SPME-MOI-MS/MS). The BioSPME-MOI-MS/MS method offers ≤ 10% imprecision of in-house prepared quality controls over a 10-day period, ≤ 10% imprecision of ClinCal® Recipe calibrators over a three-day period, and single total turnaround time of ∼ 60 min (4.5 min for high throughput). The limits of quantification were determined to be 0.8 ng mL−1 for tacrolimus, 0.7 ng mL−1 sirolimus, 1.0 ng mL−1 for everolimus, and 0.8 ng mL−1 for cyclosporine. The limits of detection were determined to be 0.3 ng mL−1 for tacrolimus, 0.2 ng mL−1 for sirolimus, 0.3 ng mL−1 for everolimus, and 0.3 ng mL−1 for cyclosporine A. The R2 values for all analytes were above 0.9992 with linear dynamic range from 1.0 mL−1 to 50.0 ng mL−1 for tacrolimus, sirolimus, and everolimus while from 2.5 ng mL−1 to 500.0 ng mL−1 for cyclosporine A. To further evaluate the performance of the present method, 95 residual whole blood samples of tacrolimus and sirolimus from patients undergoing immunosuppression therapy were used to compare the Bio-SPME-MOI-MS/MS method against a clinically validated reference method based on chemiluminescent microparticle immunoassay, showing acceptable results. Our results demonstrated that Bio-SPME-MOI-MS/MS can be considered as a suitable alternative to existing methods for the determination of immunosuppressive drugs in whole blood providing faster analysis, better selectivity and sensitivity, and a wider dynamic range than current existing approaches. Fil: Nazdrajic, Emir. University of Waterloo; Canadá Fil: Tascon, Marcos. University of Waterloo; Canadá. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; Argentina Fil: Rickert, Daniel A.. University of Waterloo; Canadá Fil: Gómez Ríos, German A.. University of Waterloo; Canadá Fil: Kulasingam, Vathany. University of Toronto; Canadá. University of Toronto; Canadá Fil: Pawliszyn, Janusz B.. University of Waterloo; Canadá |
description |
Immunosuppressive drugs are administered to decrease immune system activity (e.g. of patients undergoing solid organ transplant). Concentrations of immunosuppressive drugs (ISDs) in circulating blood must be closely monitored during the period of immunosuppression therapy due to adverse effects that take place when concentration levels fall outside of the very narrow therapeutic concentration range of these drugs. This study presents the rapid determination of four relevant immunosuppressive drugs (tacrolimus, sirolimus, everolimus, and cyclosporine A) in whole human blood by directly coupling solid-phase microextraction to mass spectrometry via the microfluidic open interface (Bio-SPME-MOI-MS/MS). The BioSPME-MOI-MS/MS method offers ≤ 10% imprecision of in-house prepared quality controls over a 10-day period, ≤ 10% imprecision of ClinCal® Recipe calibrators over a three-day period, and single total turnaround time of ∼ 60 min (4.5 min for high throughput). The limits of quantification were determined to be 0.8 ng mL−1 for tacrolimus, 0.7 ng mL−1 sirolimus, 1.0 ng mL−1 for everolimus, and 0.8 ng mL−1 for cyclosporine. The limits of detection were determined to be 0.3 ng mL−1 for tacrolimus, 0.2 ng mL−1 for sirolimus, 0.3 ng mL−1 for everolimus, and 0.3 ng mL−1 for cyclosporine A. The R2 values for all analytes were above 0.9992 with linear dynamic range from 1.0 mL−1 to 50.0 ng mL−1 for tacrolimus, sirolimus, and everolimus while from 2.5 ng mL−1 to 500.0 ng mL−1 for cyclosporine A. To further evaluate the performance of the present method, 95 residual whole blood samples of tacrolimus and sirolimus from patients undergoing immunosuppression therapy were used to compare the Bio-SPME-MOI-MS/MS method against a clinically validated reference method based on chemiluminescent microparticle immunoassay, showing acceptable results. Our results demonstrated that Bio-SPME-MOI-MS/MS can be considered as a suitable alternative to existing methods for the determination of immunosuppressive drugs in whole blood providing faster analysis, better selectivity and sensitivity, and a wider dynamic range than current existing approaches. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-02 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/160845 Nazdrajic, Emir; Tascon, Marcos; Rickert, Daniel A.; Gómez Ríos, German A.; Kulasingam, Vathany; et al.; Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface; Elsevier Science; Analytica Chimica Acta; 1144; 2-2021; 53-60 0003-2670 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/160845 |
identifier_str_mv |
Nazdrajic, Emir; Tascon, Marcos; Rickert, Daniel A.; Gómez Ríos, German A.; Kulasingam, Vathany; et al.; Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface; Elsevier Science; Analytica Chimica Acta; 1144; 2-2021; 53-60 0003-2670 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.aca.2020.11.056 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0003267020311867 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier Science |
publisher.none.fl_str_mv |
Elsevier Science |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
_version_ |
1844614144374865920 |
score |
13.070432 |