A simple, rapid and selective sample pretreatment method, molecularly imprinted matrix solid-phase dispersion (MI-MSPD) coupled with liquid chromatography, was developed for the rapid isolation of acyclovir (ACV) from edible creatural tissues. New molecularly imprinted polymer (MIP) synthesized by using theophylline as a dummy template revealed a high special affinity to ACV, and was employed as the selective dispersant of matrix solid-phase dispersion (MSPD) for the rapid screening of ACV. The presented method obviously reduced the tedious separation procedure, improved the extraction selectivity and purification efficiency, and significantly eliminated the effect of template leakage of MIP on quantitative analysis. The results indicated that the interference compounds originating from the creatural tissue matrix could be efficiently eliminated, and the elution was clean enough for HPLC analysis. Good linearity of ACV was obtained in a range of 0.10–50.0 μg g−1 with r2 = 0.9998, and the limit of quantification based on the signal to noise of 10 was 0.09 μg g−1. The recoveries at three spiked levels were in the range of 85.5–108.1% with RSD ≤ 3.7% (n = 3). The presented MI-MSPD method combined the advantages of MIP and MSPD, and could be applied for the rapid and selective screening of ACV in creatural tissues.
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