Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS

Objectives. Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination o...

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Main Authors: Mustafa Karapirli, Murat Kizilgun, Ozgur Yesilyurt, Husamettin Gul, Zeki Ilker Kunak, Emin Ozgur Akgul, Enis Macit, Tuncer Cayci, Yasemin Gulcan Kurt, Ibrahim Aydin, Hakan Yaren, Melik Seyrek, Erdinc Cakir, Halil Yaman
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/2012/571201
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author Mustafa Karapirli
Murat Kizilgun
Ozgur Yesilyurt
Husamettin Gul
Zeki Ilker Kunak
Emin Ozgur Akgul
Enis Macit
Tuncer Cayci
Yasemin Gulcan Kurt
Ibrahim Aydin
Hakan Yaren
Melik Seyrek
Erdinc Cakir
Halil Yaman
author_facet Mustafa Karapirli
Murat Kizilgun
Ozgur Yesilyurt
Husamettin Gul
Zeki Ilker Kunak
Emin Ozgur Akgul
Enis Macit
Tuncer Cayci
Yasemin Gulcan Kurt
Ibrahim Aydin
Hakan Yaren
Melik Seyrek
Erdinc Cakir
Halil Yaman
author_sort Mustafa Karapirli
collection DOAJ
description Objectives. Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples. Materials and Methods. We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients. Results. System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes. Conclusion. This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.
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spelling doaj-art-e7b5e1ee5da9440897004eefc4ecb9252025-08-20T03:21:02ZengWileyThe Scientific World Journal1537-744X2012-01-01201210.1100/2012/571201571201Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MSMustafa Karapirli0Murat Kizilgun1Ozgur Yesilyurt2Husamettin Gul3Zeki Ilker Kunak4Emin Ozgur Akgul5Enis Macit6Tuncer Cayci7Yasemin Gulcan Kurt8Ibrahim Aydin9Hakan Yaren10Melik Seyrek11Erdinc Cakir12Halil Yaman13Council of Forensic Medicine, Ankara Branch, Kecioren, 06018 Ankara, TurkeyDepartment of Biochemistry, Diskapi Children' Health and Diseases, Hematology, Oncology Training and Research Hospital, Ministry of Health, 06590 Ankara, TurkeyDepartment of Pharmacology, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Pharmacology, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Medical Chemical/Biological/Radiological/Nuclear Defense, Gulhane Military Medical Academy, Etlik, 06018 Ankara, TurkeyDepartment of Clinical Biochemistry, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Pharmacology, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Clinical Biochemistry, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Clinical Biochemistry, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Clinical Biochemistry, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Medical Chemical/Biological/Radiological/Nuclear Defense, Gulhane Military Medical Academy, Etlik, 06018 Ankara, TurkeyDepartment of Pharmacology, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Clinical Biochemistry, Gulhane Military Medical Academy, 06018 Ankara, TurkeyDepartment of Clinical Biochemistry, Gulhane Military Medical Academy, 06018 Ankara, TurkeyObjectives. Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples. Materials and Methods. We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients. Results. System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes. Conclusion. This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.http://dx.doi.org/10.1100/2012/571201
spellingShingle Mustafa Karapirli
Murat Kizilgun
Ozgur Yesilyurt
Husamettin Gul
Zeki Ilker Kunak
Emin Ozgur Akgul
Enis Macit
Tuncer Cayci
Yasemin Gulcan Kurt
Ibrahim Aydin
Hakan Yaren
Melik Seyrek
Erdinc Cakir
Halil Yaman
Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS
The Scientific World Journal
title Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS
title_full Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS
title_fullStr Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS
title_full_unstemmed Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS
title_short Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS
title_sort simultaneous determination of cyclosporine a tacrolimus sirolimus and everolimus in whole blood samples by lc ms ms
url http://dx.doi.org/10.1100/2012/571201
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