Deep eutectic solvent-based hollow fiber liquid-phase microextraction for quantification of Q-markers of cinnamic acid derivatives in traditional Chinese medicines and research of their plasma protein binding rates

A deep eutectic solvent-based hollow fiber liquid-phase microextraction was proposed and coupled with high performance liquid chromatography-ultraviolet detection for the quantification of four cinnamic acid derivatives (caffeic acid, p-hydroxycinnamic acid, ferulic acid, cinnamic acid) in traditional Chinese medicines and research of their plasma protein binding rates. Also, the extraction mechanism of target analytes and the determination mechanism of their plasma protein binding rate by the procedure are both explored and illustrated. In this study, the variables affecting the experiment procedure, including the type and composition of deep eutectic solvent, sample phase pH, salt amount, extraction temperature, stirring rate, extraction time, and incubation time of active compound in plasma (i.e., binding equilibrium time between active compound and plasma protein) were investigated and optimized. Under the optimum conditions, enrichment factors of 82.4, 105.9, 88.8, 127.1 for caffeic acid, p-hydroxycinnamic acid, ferulic acid and cinnamic acid, satisfactory linear ranges (r2 ≥ 0.9985), low detection limits (0.1–0.3 ng/mL), acceptable precisions with relative standard deviations (0.7%–6.1%) and recoveries (between 86.7% and 110.5%) were obtained. The feasibility of the proposed method was evaluated by the determination of four analytes in Chinese medicinal samples and research of their plasma protein binding rates. The results indicated that the developed method is eco-friendly, easy-to-handle, and has the major advantages of high-preconcentration factor and remarkable clean-up ability.