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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/160845

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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
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