Simultaneous determination of cyclosporine A, tacrolimus, sirolimus, and everolimus in whole-blood samples by LC-MS/MS.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Council of Forensic Medicine, Ankara Branch, Kecioren, 06018 Ankara, Turkey.
Mustafa
M
Karapirli
Murat
M
Kizilgun
Ozgur
O
Yesilyurt
Husamettin
H
Gul
Zeki Ilker
ZI
Kunak
Emin Ozgur
EO
Akgul
Enis
E
Macit
Tuncer
T
Cayci
Yasemin
Y
Gulcan Kurt
Ibrahim
I
Aydin
Hakan
H
Yaren
Melik
M
Seyrek
Erdinc
E
Cakir
Halil
H
Yaman
D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid; D016572:Cyclosporine / Q000097:blood*; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D013058:Mass Spectrometry / Q000379:methods*; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood*; D016559:Tacrolimus / Q000097:blood*; D019737:Transplants
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus