Establishment of a blood concentration detection system for everolimus in recipients after liver transplantation
10.3969/j.issn.1674-7445.2021.05.014
- VernacularTitle:肝移植术后受者依维莫司血药浓度检测体系的建立
- Author:
Simei TAO
1
;
Jiwei HUANG
;
Haibo LI
;
Yingcai ZHANG
;
Yang YANG
Author Information
1. Department of Pharmacy, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
- Publication Type:Research Article
- Keywords:
Everolimus;
Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS);
High performance liquid chromatography (HPLC);
Liver transplantation;
Blood concentration;
Calcineurin inhibitor (CNI);
Mammalian target of rapamycin (mTOR);
Sirolimus
- From:
Organ Transplantation
2021;12(5):595-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a detection system of ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for everolimus concentration in whole blood of liver transplant recipients. Methods The proteins of samples were precipitated with methanol and zinc sulfate, and everolimus-D4 was used as the internal standard. Phenomenex Kinetex PFP column was used. The mobile phase A was water (containing 2 mmol/Lammonium formate and 0.1% formic acid), and the mobile phase B was methanol (containing 2 mmol/L ammonium formate and 0.1% formic acid). The gradient elution was performed with the flow rate of 1 mL/min, the column temperature of 50 ℃ and the injection volume of 1 μL. The multi-reaction monitoring mode was used to quantitatively analyze with electrospray positive ionization. The UPLC-MS/MS detection system required only 100 μL of whole blood, and could achieve a sufficient lower limit of quantification without complicated sample preparation. The total running time was within 4.5 min. Linear regression (1/x2) analysis was performed using peak area of everolimus / peak area of everolimus-D4 (y) and concentration of everolimus/concentration of everolimus-D4 (x) to calculate the calibration function and analyze its accuracy and linear relationship. UPLC-MS/MS was used to detect the trough blood concentration of everolimus in blood samples of 5 recipients after liver transplantation. Results The accuracy of quality control was within 15%, and the linear relationship of everolimus was good in the blood concentration range of 1-100 ng /mL(R2 > 0.990). Trough blood concentration of everolimus measured in blood samples of 5 liver transplant recipients ranged from 3.77 to 9.27 ng/mL. Conclusions The detection system of UPLC-MS/MS in this study is suitable for monitoring the concentration of everolimus in whole blood of liver transplant recipients because of its high accuracy, simple sample processing method and short detection time.
