Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients

Background: Measurement of trough levels for calcineurin inhibitors by venipuncture sampling is a mainstay of patient management in solid organ transplant recipients but challenging in pediatric patients. Volumetric Absorptive Microsampling (VAMS) is a patient-friendly, minimally invasive sampling t...

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Main Authors: Junfang Zhao, Kenneth D.R. Setchell, Xueheng Zhao, Stephanie Galandi, BreAnn N Garr, Zhiqian Gao, Clifford Chin, Shelly Stark, Paul E. Steele, Thomas D. Ryan
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Journal of Mass Spectrometry and Advances in the Clinical Lab
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667145X2300038X
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author Junfang Zhao
Kenneth D.R. Setchell
Xueheng Zhao
Stephanie Galandi
BreAnn N Garr
Zhiqian Gao
Clifford Chin
Shelly Stark
Paul E. Steele
Thomas D. Ryan
author_facet Junfang Zhao
Kenneth D.R. Setchell
Xueheng Zhao
Stephanie Galandi
BreAnn N Garr
Zhiqian Gao
Clifford Chin
Shelly Stark
Paul E. Steele
Thomas D. Ryan
author_sort Junfang Zhao
collection DOAJ
description Background: Measurement of trough levels for calcineurin inhibitors by venipuncture sampling is a mainstay of patient management in solid organ transplant recipients but challenging in pediatric patients. Volumetric Absorptive Microsampling (VAMS) is a patient-friendly, minimally invasive sampling technique to accurately collect blood. An assay for measurement of tacrolimus in blood using VAMS, coupled with parallel reaction monitoring (PRM) mass spectrometry, was validated in pediatric heart transplant patients. Methods: Tacrolimus was measured by a newly developed high-resolution PRM assay and compared with low-resolution tandem mass spectrometry (MRM). Dried blood samples were collected from pediatric heart transplant patients (n = 35) using VAMS devices and a satisfaction survey was completed by patients/guardians. Tacrolimus concentrations were compared across whole liquid blood, dried blood spots, and capillary blood, and shipping stability determined. Results: The PRM assay was linear over a range 1–50 ng/mL, similar to MRM but had greater specificity due to reduced background noise. No significant differences in tacrolimus concentrations were observed between VAMS and venous blood. Tacrolimus dried on VAM tips was stable for 14 days and concentrations were unaffected by postal shipping. The variability in two simultaneously collected at-home patient samples was minimal – average concentration difference was 0.12 ± 0.94 ng/mL (p = 0.6) between paired samples. Conclusion: A high resolution PRM mass spectrometry assay was developed for home-based dried blood collections for therapeutic monitoring of tacrolimus. The advantage of PRM was enhanced specificity and the VAMS devices provided a simple and convenient approach to blood sampling at home in pediatric heart transplant patients.
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spelling doaj.art-f4f4d791993b474fbe60cfe5fe13252c2024-02-09T04:49:27ZengElsevierJournal of Mass Spectrometry and Advances in the Clinical Lab2667-145X2024-01-013117Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patientsJunfang Zhao0Kenneth D.R. Setchell1Xueheng Zhao2Stephanie Galandi3BreAnn N Garr4Zhiqian Gao5Clifford Chin6Shelly Stark7Paul E. Steele8Thomas D. Ryan9Division of Pathology & Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USADivision of Pathology & Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Corresponding authors at: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.Division of Pathology & Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USADivision of Pathology & Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USAHeart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USAHeart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USAHeart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USAHeart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USADivision of Pathology & Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USAHeart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Corresponding authors at: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.Background: Measurement of trough levels for calcineurin inhibitors by venipuncture sampling is a mainstay of patient management in solid organ transplant recipients but challenging in pediatric patients. Volumetric Absorptive Microsampling (VAMS) is a patient-friendly, minimally invasive sampling technique to accurately collect blood. An assay for measurement of tacrolimus in blood using VAMS, coupled with parallel reaction monitoring (PRM) mass spectrometry, was validated in pediatric heart transplant patients. Methods: Tacrolimus was measured by a newly developed high-resolution PRM assay and compared with low-resolution tandem mass spectrometry (MRM). Dried blood samples were collected from pediatric heart transplant patients (n = 35) using VAMS devices and a satisfaction survey was completed by patients/guardians. Tacrolimus concentrations were compared across whole liquid blood, dried blood spots, and capillary blood, and shipping stability determined. Results: The PRM assay was linear over a range 1–50 ng/mL, similar to MRM but had greater specificity due to reduced background noise. No significant differences in tacrolimus concentrations were observed between VAMS and venous blood. Tacrolimus dried on VAM tips was stable for 14 days and concentrations were unaffected by postal shipping. The variability in two simultaneously collected at-home patient samples was minimal – average concentration difference was 0.12 ± 0.94 ng/mL (p = 0.6) between paired samples. Conclusion: A high resolution PRM mass spectrometry assay was developed for home-based dried blood collections for therapeutic monitoring of tacrolimus. The advantage of PRM was enhanced specificity and the VAMS devices provided a simple and convenient approach to blood sampling at home in pediatric heart transplant patients.http://www.sciencedirect.com/science/article/pii/S2667145X2300038XTacrolimusVolumetric absorptive microsamplingParallel reaction monitoringPediatric heart transplant patients
spellingShingle Junfang Zhao
Kenneth D.R. Setchell
Xueheng Zhao
Stephanie Galandi
BreAnn N Garr
Zhiqian Gao
Clifford Chin
Shelly Stark
Paul E. Steele
Thomas D. Ryan
Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients
Journal of Mass Spectrometry and Advances in the Clinical Lab
Tacrolimus
Volumetric absorptive microsampling
Parallel reaction monitoring
Pediatric heart transplant patients
title Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients
title_full Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients
title_fullStr Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients
title_full_unstemmed Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients
title_short Use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients
title_sort use of volumetric absorptive microsampling and parallel reaction monitoring mass spectrometry for tacrolimus blood trough measurements at home in pediatric heart transplant patients
topic Tacrolimus
Volumetric absorptive microsampling
Parallel reaction monitoring
Pediatric heart transplant patients
url http://www.sciencedirect.com/science/article/pii/S2667145X2300038X
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