Molecularly imprinted polymer for the selective extraction of cocaine and its metabolites, benzoylecgonine and ecgonine methyl ester, from biological fluids before LC–MS analysis

• Highly selective extraction of COC and its metabolites from acetonitrile media.
• Selective extraction of COC from serum and urine with high recoveries on the MIP.
• Low retention of the polar metabolites in real samples.
• Efficient clean-up of urine extracts before the analysis of the three target analytes.

Considering the important complexity of biological samples, a molecularly imprinted polymer (MIP) was applied to the selective extraction of cocaine and its two main metabolites, benzoylecgonine and ecgonine methyl ester from biological samples. The MIP was imprinted with cocaine and it was synthesized in acetonitrile with methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a crosslinker. The selectivity of the MIP was first assessed for the three target analytes in acetonitrile with recoveries higher than 80% on the MIP and lower than 30% on the non-imprinted polymer (NIP). The MIP was then evaluated for the selective extraction of these targets from real aqueous media, i.e. serum and urine samples. The pH adjustment of the sample as well as the optimization of the washing step led to a very selective extraction of cocaine from these media. A LOQ of 0.5 ng/mL was obtained for cocaine in urine. Concerning cocaine metabolites, benzoylecgonine and ecgonine methyl ester, they were first extracted from urine by liquid–liquid extraction and the resulting extract was purified on the MIP. The results obtained with the MIP as compared to the LLE alone showed the great potential of the MIP extraction for the clean-up of the biological matrix. This procedure was tested for the extraction of the analytes from urine samples, leading to a very selective protocol with LOQs of 0.09 ng/mL, 0.4 ng/mL and 1.1 ng/mL for cocaine, benzolecgonine and ecgonine methyl ester respectively in urine samples.