Magnetic molecularly imprinted polymer based – micro-solid phase extraction of cocaine and metabolites in plasma followed by high performance liquid chromatography – tandem mass spectrometry

• Magnetic molecularly imprinted polymer (MMIP) for cocaine and metabolites
• Batch μ-SPE for treating small volumes of samples
• Fast cocaine and metabolites determination by reverse phase HPLC-MS/MS
• Limit of quantification lower than the cut-off values for cocaine abuse confirmation

A novel adsorbent, magnetic molecularly imprinted polymer (MMIP) based on magnetite nanoparticles surface-covered with an MIP selective for cocaine (COC), was synthesised and used in batch micro-solid phase extraction (μ-SPE) for isolation of COC and metabolites (benzoylecgonine, BZE; cocaethylene, CE; and ecgonine methyl ester, EME) from plasma samples. High performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) was used for performing analysis. Parameters such as sample pH, magnetic stirring speed, extraction temperature and time (loading stage), composition and volume of the eluting solution, and desorption time, were optimised. Under the most favourable conditions, the highest extraction yields were obtained by using 0.1 to 1.0 mL of plasma (pH adjusted at 8.5) plus 50 mg of MMIP, and magnetic stirring (20 °C, 100 rpm) for 4 min. Elution was performed with 2 mL of a dichloromethane/2-propanol/ammonium hydroxide (75:20:5) mixture under ultrasound irradiation (325 W, 35 kHz) for 5 min. The limits of detection were between 0.013 and 0.36 ng L− 1, and the limits of quantification were from 0.043 to 1.2 ng L− 1. The relative standard deviations of intra- and inter-day tests (three concentration levels tested) ranged from 1 to 9% and from 2 to 10%, respectively. Analytical recoveries were in the range of 91–102% when spiking drug-free plasma samples at three concentration levels. Accurate results were also obtained after analysing a BTMF 1/11-B control material.