Herein, for the first time, an acidic DES comprised of malonic acid and ChCl was used to complete dissolution of Co-Al, Ni-Al, and Cu-Al LDHs as sorbents in the vortex assisted in-situ solid phase extraction of doxepin and amitriptyline followed by HPLC-UV. Moreover, the ability of urea: ChCl and ethylene glycol: ChCl was investigated to dissolve the LDH sorbents. The optimized extraction conditions were obtained at a vortex time of 2 min, 4:2 molar ratio of Co2+:Al3+ , 0.81 mol L–1 NaOH, and 65 µL of acidic DES based on the BBD. The linearity, LOD, and R2 for both analytes were in the range of 1–400 μg L-1 , 0.69–0.84 μg L-1 , and 0.995–0.999, respectively. The recoveries of more than 93.1% with RSDs of less than 5.3% were achieved for spiking urine and pharmaceutical formulation samples.
