Trace Determination of Duloxetine in Human Plasma by a Novel Ionic Liquid-Based Ultrasound-Assisted In Situ Solvent Formation Microextraction and High-Performance Liquid Chromatography

For the first time, a novel and efficient ionic liquid-based ultrasound-assisted in-situ solvent formation microextraction (IL-UA-ISFME) combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) has been successfully developed for the determination of duloxetine (DLX) in human plasma. Herein, an environmentally-friendly hydrophobic ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate) was formed by addition of a hydrophilic ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate) to sample solution including NaPF6 as an ion-pairing agent. The analyte was extracted into the ionic liquid although the microextraction solvent was dispersed among the sample solution using ultrasound radiation. The sample was then centrifuged and extracting phase injected into HPLC system. The developed sample enrichment method revealed considerable robustness against the variations of sample ionic strength. Begin with, parameters controlling the performance of the microextraction were evaluated and optimized. The limit of detection was 0.8 µg L-1 while a good linearity (r2 = 0.996) and a broad linear range (2.0 to 1500 µg L-1) were achieved. A reasonable relative recoveries (83.6-92.1%) and appropriate intra-assay (4.0-5.1%, n = 5) and inter-assay (4.3-7.6%, n = 9) precisions along with appropriate sample clean-up exhibited good performance of the analytical procedure. It was eventually validated for the screening purposes in human plasma after oral administration of the drug and some pharmacokinetic data were achieved. This green method is prompt, convenient, and reliable and offers satisfactory reproducibility as well as sufficient sensitivity.