Mass spectrometry quantitation of immunosuppressive drugs in clinical specimens using online solid-phase extraction and accurate-mass full scan-single ion monitoring

Autor: Priscilla S.-W. Yeung, Paige Miller, Tran Bao Lai-Nyugen, Phil Cheng, Amira Ibrahim, Run-Zhang Shi, Raffick A.R. Bowen, Ruben Yiqi Luo
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Mass Spectrometry and Advances in the Clinical Lab, Vol 28, Iss , Pp 99-104 (2023)
Druh dokumentu: article
ISSN: 2667-145X
DOI: 10.1016/j.jmsacl.2023.03.002
Popis: Introduction: Therapeutic drug monitoring (TDM) of immunosuppressants is essential for optimal care of transplant patients. Immunoassays and liquid chromatography-mass spectrometry (LC-MS) are the most commonly used methods for TDM. However, immunoassays can suffer from interference from heterophile antibodies and structurally similar drugs and metabolites. Additionally, nominal-mass LC-MS assays can be difficult to optimize and are limited in the number of detectable compounds. Objectives: The aim of this study was to implement a mass spectrometry-based test for immunosuppressant TDM using online solid-phase extraction (SPE) and accurate-mass full scan-single ion monitoring (FS-SIM) data acquisition mode. Methods: LC-MS analysis was performed on a TLX-2 multi-channel HPLC with a Q-Exactive Plus mass spectrometer. TurboFlow online SPE was used for sample clean up. The accurate-mass MS was set to positive electrospray ionization mode with FS-SIM for quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A. MS2 fragmentation pattern was used for compound confirmation. Results: The method was validated in terms of precision, analytical bias, limit of quantitation, linearity, carryover, sample stability, and interference. Quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A correlated well with results from an independent reference laboratory (r = 0.926–0.984). Conclusions: Accurate-mass FS-SIM can be successfully utilized for immunosuppressant TDM with good correlation with results generated by standard methods. TurboFlow online SPE allows for a simple “protein crash and shoot” sample preparation protocol. Compared to traditional MRM, analyte quantitation by FS-SIM facilitates a streamlined assay optimization process.
Databáze: Directory of Open Access Journals