Please cite this article in press as: M.R. Gama, C.B.G. Bottoli, Molecularly imprinted polymers for bioanalytical sample preparation, J. Chromatogr. B (2016), http://dx.doi.org/10.1016/j.jchromb.2016.09.045 ARTICLE IN PRESS G Model CHROMB-20301; No. of Pages 15 Journal of Chromatography B, xxx (2016) xxx–xxx Contents lists available at ScienceDirect Journal of Chromatography B jou rn al hom ep age: www.elsevier.com/locate/chromb Molecularly imprinted polymers for bioanalytical sample preparation Mariana Roberto Gama, Carla Beatriz Grespan Bottoli * Institute of Chemistry - State University of Campinas, Unicamp, Brazil a r t i c l e i n f o Article history: Received 28 June 2016 Received in revised form 20 September 2016 Accepted 23 September 2016 Available online xxx Keywords: Molecularly imprinted polymers Sorbents Biomarkers Metabolites Bioanalysis a b s t r a c t Molecularly imprinted polymers (MIP) are stable polymers with molecular recognition abilities, provided by the presence of a template during their synthesis, and are excellent materials with high selectivity for sample preparation in bioanalytical methods. This short review discusses aspects of MIP preparation and its applications as a sorbent material in pharmaceutical and biomedical analysis. MIP in different extraction configurations, including classical solid-phase extraction, solid-phase microextraction, mag- netic molecularly imprinted solid-phase extraction, microextraction by packed sorbent and solid-phase extraction in pipette tips, are used to illustrate the good performance of this type of sorbent for sample preparation procedures of complex matrices, especially prior to bioanalytical approaches. © 2016 Elsevier B.V. All rights reserved. 1. Introduction High-throughput bioanalyses are essential to support drug dis- covery and are used for analysis for metabolites and biomarkers, while plasma, urine and cerebrospinal fluid are the most com- mon biological sample matrices. Despite the high detectability and selectivity of current analytical techniques for quantifying target analytes in biological fluids, biological samples are not usually directly introduced into a chromatographic system without a pre- treatment step. Abbreviations: MIP, molecularly imprinted polymer; LLE, liquid–liquid extrac- tion; SPE, solid-phase extraction; SPME, solid-phase microextraction; MISPE, molecularly imprinted solid-phase extraction; MMISPE, magnetic molecularly imprinted solid-phase extraction; MSPD, matrix solid-phase dispersion; MEPS, microextraction by packed sorben; RAMIP-BSA, restricted access molecularly imprinted polymer coated with bovine serum albumin; SBSE, stir-bar sorptive extraction; PT-SPE, solid-phase extraction in pipette tips; MAA, methacrylic acid; EGDMA, ethylene glycol dimethacrylate; DVB, divinyl benzene; TRIM, trimethylol propane trimethacrylate; DMSO, dimethyl sulfoxide; THF, tetrahydrofuran; NOBE, N,O-bismethacryloylethanolamine; PETA, pentaerythrol triacrylate; PETEA, pen- taerythrol tetraacrylate; CEC, capillary electrochromatography; DAD, diode array detector; FL, fluorescence; LOD, limit of detection; LOQ, limit of quantification; RAM, restricted access material; BSA, bovine serum albumin; CSF, cerebrospinal fluid; MALDI, matrix-assisted laser desorption/ionization; TOF, time-of-flight; MS, mass spectrometry; MS/MS, tandem mass spectrometry; UHPLC, ultra high performance liquid chromatography. * Corresponding author. E-mail address: carlab@iqm.unicamp.br (C.B.G. Bottoli). The goals of sample preparation in bioanalytical methods are to: (i) minimize matrix effects, by the reduction of ion suppres- sion; (ii) eliminate sample variability, to achieve more reproducible quantitation even from different sources and to improve method robustness; (iii) increase detectivity, through analyte concentra- tion and removal of interferences from the biological matrices; and (iv) clean samples, in order to increase both instrument uptime and system performance. Liquid-liquid extraction (LLE), protein precipitation and solid- phase extraction (SPE) are used to isolate and concentrate analytes from biological matrices. Protein precipitation is fast, requires little method development and is cost-effective. However, this method only removes proteins from samples, leaving behind other interfer- ences that can negatively affect the analysis and column lifetime. Traditional LLE removes proteins, phospholipids and salts, but it is time-consuming and difficult to automate, which limits its throughput capability [1–3]. Sample extraction by SPE has gained in popularity because of its compatibility with automation, especially with sorbent mate- rial packed into a 96-well format plate. Advances in SPE include the development of on-line procedures, polymeric sorbents that no longer suffer from sorbent drying problems while enjoying extended working pH ranges, and high affinity sorbents, such as molecularly imprinted polymers (MIP). This short review describes the MIP, discussing aspects of its preparation and its applications as sorbent material for sample preparation routines in bioanalytical methods. Recent pharma- ceutical and biomedical applications of MIP in different SPE configurations are also presented to illustrate the good perfor- http://dx.doi.org/10.1016/j.jchromb.2016.09.045 1570-0232/© 2016 Elsevier B.V. All rights reserved.