Evidence map›Paper›PMID 40401811›Full record

ArticleTherapeutic drug monitoring2025

An Offline SPE-LC-MS/MS Method for Simultaneous Quantification of Tacrolimus, Cyclosporine A, Kynurenine, Tryptophan, and Creatinine Using Volumetric Absorptive Microsampling Device Mitra.

Kajetan Nierychlewski, Katharina Habler, Stephan Kemmner, Tobias Seibt, Michael Fischereder, Markus Schwarz

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Article in Therapeutic drug monitoring, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Kajetan NierychlewskiInstitute of Laboratory Medicine, LMU University Hospital, LMU Munich, Germany.
Katharina HablerInstitute of Laboratory Medicine, LMU University Hospital, LMU Munich, Germany.
Stephan KemmnerTransplant Center, LMU University Hospital, LMU Munich, Germany ; and.
Tobias SeibtTransplant Center, LMU University Hospital, LMU Munich, Germany ; and.
Michael FischerederRenal Division, Department of Internal Medicine IV, LMU University Hospital, LMU Munich, Germany .
Markus SchwarzInstitute of Laboratory Medicine, LMU University Hospital, LMU Munich, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTherapeutic drug monitoring of immunosuppressants is critical in balancing insufficient immunosuppression due to underdosing, and severe adverse effects due to overdosage. For a more comprehensive therapeutic drug monitoring and follow-up of transplant patients, the aim was to develop a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of tacrolimus, cyclosporine A, tryptophan, kynurenine, and creatinine using a volumetric absorptive microsampling device.

methodsVenous and capillary blood samples were simultaneously collected using a volumetric absorptive microsampling device called Mitra. The method involved protein precipitation followed by offline solid-phase extraction using a positive pressure manifold. Chromatographic separation was achieved by a formic acid-ammonium formate-methanol gradient on a Synergi Polar reversed-phase column. Multiple reaction monitoring in the positive ion mode and stable isotope-labeled internal standards were used for quantification. Validation was performed according to the European Medicines Agency and US Food and Drug Administration (FDA) guidelines.

resultsValidation was successful, meeting European Medicines Agency and FDA guidelines. Investigation of selectivity, accuracy, and precision met the required criteria of a deviation <15%. Internal standards successfully compensated potential matrix effects. A comparison of 26 anonymized samples from transplant patients on Mitra with venous blood controls demonstrated the method's suitability.

conclusionsFor the first time, we herein describe a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of tacrolimus, cyclosporine A, tryptophan, kynurenine, and creatinine on Mitra. Self-collection of samples may facilitate therapeutic monitoring. Simultaneous determination of creatinine may help monitor kidney function, while tryptophan and kynurenine may serve as a biomarker for early detection of transplant rejection.

Indexed as

CreatinineCyclosporineImmunosuppressive AgentsKynurenineTacrolimusTryptophanBlood Specimen CollectionChromatography, LiquidDrug MonitoringHumansLiquid Chromatography-Mass SpectrometryReproducibility of ResultsSolid Phase ExtractionTandem Mass SpectrometryCreatinineCyclosporineImmunosuppressive AgentsKynurenineTacrolimusTryptophanhigh-performance liquid chromatography–tandem mass spectrometryimmunosuppressantskynurenine pathwaytherapeutic drug monitoringvolumetric absorptive microsampling device

Identifiers

PMID40401811
PMCPMC12422614

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.