Preparation of covalent organic frameworks combined with metal organic frameworks and their application in extraction of cyclosporine and tacrolimus from biological samples prior to their determination by liquid chromatography coupled with mass spectrometry

Abstract

Cyclosporine and tacrolimus are immunosuppressants drugs witch are used to prevent organ transplant rejection and treat autoimmune diseases. Due to their narrow and unpredictable therapeutic window, it is essential to measure their plasma concentration. Analytical methods in biological samples are recommended for monitoring these drugs. However, analyzing them in biological samples requires sample preparation to clean and pre-concentrate the samples, making this step indispensable for accurate analysis.Purpose:The purpose of this study was to develop a simple, sensitive, and effective method for the determination of cyclosporine and tacrolimus in biological samples using high-Performance liquid chromatography coupled with Tandem Mass Spectrometry. For this purpose, UiO-66 metal-organic framework was synthesized hydrothermally and incorporated with covalent-organic framework based on benzidine. Then it was used as the sorbent in extraction of the analytes from biological and water samples.Methods:For this purpose, after adding a proper amount of the sorbent into the sample solution, the mixture was sonicated for 5 min. To collect the sorbent, the mixture was centrifuged and the supernatant was removed. To desorb the desired analyte, the sorbent was eluted with 200 μL mixture of 90% acetonitrile and 10% deionized water and was vortexed for 5 min. Then, the eluent was injected into the HPLC-MS/MS for quantitative analysis. Results:The method provided satisfactory results, including low limits of detection and quantification, accepatble relative standard deviations, and a wide linear range. Finally, the proposed method was utilized as a sensitive method on biological samples including plasma and urine samples.Conclusions:This study has completely fulfilled its purpose; therefore, the proposed method can be successfully applied as a simple, sensitive, and cost-effective method in routine analysis for the determination of cyclosporine and tacrolimus in plasma and urine samples.