Development of Dioctyl Phthalate@Fe3O4 Nanocomposite Reinforced Hollow
Fiber Solid/ Liquid Phase Microextraction Followed by HPLC-DAD
for the Determination of Atorvastatin and Gemfibrozil in Human Urine
Authors: AL-Hashimi Nabil N. , Shtaiwi Majed H. , Hamed Saja H. , El-Sheikh Amjad H. , Shahin Rand O. , Banisakher Linda S. , Tahboub Dua'a M. 
Published: December 2021

Background:
The desirable levels of lipids, especially in patients with coronary artery
disease, might not be achievable with a single lipid-lowering drug; thus, combination therapy using
atorvastatin and gemfibrozil seems to be a promising approach. However, the potential for drugdrug
interaction needs to be taken into consideration, and the combination (atorvastatin and gemfibrozil)
is recommended only when other options for reducing lipids have been exhausted.

Objectives:
Many studies are conducted for the determination of atorvastatin or gemfibrozil in biological
fluids and tablets; however, the simultaneous determination of the two drugs in complex biological
matrices is limited. Consequently, the development of a sensitive method for simultaneous
determination of atorvastatin and gemfibrozil in urine samples is urgently needed to make sure that
the doses of both medications are given to patients correctly to prevent the risk of side effects outcomes
associated with the adverse drug-drug interaction.

Methods:
Methods: A synthesized nanocomposite sorbent, dioctyl phthalate coated on the surface of magnetite
(DOP@Fe3O4), was reinforced and immobilized into the pores of 2.5 cm segment hollow
fiber microtube via ultrasonication, and the lumen of the microtube was filled with 1-octanol as an
organic solvent with two ends heat-sealed. The prepared (DOP@Fe3O4-HF-SLPME) device was directly
immersed into 10 mL of a sample solution containing atorvastatin and gemfibrozil with agitation.
Subsequently, the microextraction device was transferred to HPLC-micro-vial containing an
appropriate solvent, and the selected analytes were desorbed under ultrasonication prior to HPLCDAD
analysis. The main factors influencing the adsorption and desorption process of the selected
drugs have been optimized.

Results:
Results: The DOP@Fe3O4-HF-SLPME combined with the HPLC-DAD method was analytically
evaluated for the simultaneous determination of atorvastatin and gemfibrozil in human urine samples
using the optimized conditions. In spiked urine samples, the method showed a good linearity
R2˃ 0.998, RSD from 1.41- 5.33%, and the limits of detection/ quantification (LOD/ LOQ) were
0.11/ 0.36 and 0.73/ 2.42 μg L-1 for atorvastatin and gemfibrozil, respectively. The enrichment factors
of atorvastatin and gemfibrozil were 83.4 and 101.2, with extraction recoveries of 80.9% and
99.0%, respectively. The developed method demonstrated comparable results against referenced
methods and a satisfactory result for determining the selected drugs in the patient’s urine samples.

Conclusion:
Conclusion: The DOP@Fe3O4-HF-SLPME followed by HPLC-DAD was proved to be an efficient,
sensitive, and cost-effective biopharmaceutical analysis method for trace levels of atorvastatin
and gemfibrozil in the biological fluid matrix.