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Integration of Miniaturized Solid Phase Extraction and LC-MS/MS Detection of 3-Nitrotyrosine in Human Urine for Clinical Applications
Published on: July 14, 2017
Effervescent tablet-assisted deep eutectic solvent based on magnetic nanofluid for liquid phase microextraction of
Khosrou Abdi1,2, Maryam Ezoddin3, Laleh Adlnasab4
1Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Background:
Tyrosine kinase inhibitors (TKIs) are efficient anti-cancer drugs. The analysis of TKIs in the treatment of cancer is important to achieve the highest anti-cancer effects with minimal toxicities. Herein, we report an efficient effervescent tablet-assisted deep eutectic solvent based on nanofluid (ETA-DES-NF) combined with HPLC-UV for the determination of three anti-cancer drugs (erlotinib, imatinib, and nilotinib) in human plasma samples.
Methods:
In this method, a magnetic nanofluid composed of deep eutectic solvent (DES) and Fe3O4@SiO2 nanoparticles was used as an extraction solvent. The deep eutectic solvent acted as a carrier and stabilizer for Fe3O4@SiO2 nanoparticles. A tablet was used in the nanofluid for dispersion. The effervescent tablet was implemented to generate in situ CO2 and provide the effective dispersion of the sorbent into the sample solution for diminishing the extraction time and improving the extraction efficiency. Moreover, the magnetic nanofluid enhanced phase separation efficiency without centrifugation to collect the organic solvent.
Results:
The synthesized nanofluid was characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and vibrating sample magnetometry (VSM). The impact of main parameters, including the type and volume of DES, the composition of the tablet, the composition of the nanofluid and the composition of eluent, were optimized. According to the optimized conditions, the limits of detection (LODs) and the limits of quantitation (LOQs) were from 0.5-0.8 to 1.5-2.4 μg L-1 for imatinib, erlotinib, and nilotinib, respectively. The intra-day and inter-day relative standard deviations (RSD% n = 5) were determined to be 3.1-5% and 6.4-7.5%, respectively.
Conclusions:
The developed method displayed high sensitivity, low consumption of solvent, low cost, simplicity, high recoveries, short extraction time, and good repeatability for determination of three anti-cancer drugs in human plasma samples.
Insights
A novel effervescent tablet-assisted deep eutectic solvent nanofluid method efficiently determines tyrosine kinase inhibitors (TKIs) like erlotinib and imatinib in plasma. This technique offers high sensitivity and rapid analysis for cancer drug monitoring.
Area of Science:
- Analytical Chemistry
- Nanotechnology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKIs) are crucial anti-cancer drugs requiring precise analysis for efficacy and safety.
- Optimizing TKI treatment involves balancing anti-cancer effects with minimal toxicity.
- Accurate determination of TKIs in biological samples is essential for therapeutic drug monitoring.
Purpose of the Study:
- To develop and validate an efficient method for determining three key TKIs (erlotinib, imatinib, nilotinib) in human plasma.
- To utilize an innovative effervescent tablet-assisted deep eutectic solvent-based nanofluid for sample preparation.
- To combine this novel extraction technique with High-Performance Liquid Chromatography-Ultraviolet (HPLC-UV) detection.
Main Methods:
- A magnetic nanofluid was prepared using a deep eutectic solvent (DES) and Fe3O4@SiO2 nanoparticles for extraction.
- An effervescent tablet was employed for in-situ CO2 generation, ensuring rapid and efficient dispersion of the magnetic nanofluid.
- The method facilitated magnetic separation, eliminating the need for centrifugation and reducing extraction time.
Main Results:
- The synthesized nanofluid was thoroughly characterized using FT-IR, XRD, EDX, SEM, and VSM.
- Optimization of key parameters (DES type/volume, tablet composition, nanofluid composition, eluent) was performed.
- The method achieved low limits of detection (0.5-0.8 μg L−1) and quantitation (1.5-2.4 μg L−1) with good precision (RSD < 7.5%).
Conclusions:
- The developed ETA-DES-NF combined with HPLC-UV offers a highly sensitive and efficient approach for TKI determination in plasma.
- The method is characterized by low solvent consumption, cost-effectiveness, simplicity, and short extraction times.
- It demonstrates high recoveries and good repeatability, making it suitable for routine analysis and therapeutic drug monitoring.

