In this study, the capability of electrospray ionization-ion mobility spectrometry (ESI-IMS) was investigated for detecting and measuring of pioglitazone, as an anti-diabetic drug. In this regard, pioglitazone was analyzed by ESI-IMS in both positive and negative modes of IMS. The obtained low detection limits for positive and negative modes, were 20 and 8 ng/mL for the determination of pioglitazone. In this work, molecularly imprinted polymer (MIP) was used for extraction of pioglitazone from the cow plasma. Methacrylic acid, as a functional monomer, ethylene glycol dimethylacrylat, as cross-linker, 2,2'-azobis (2-methyl propionitrile), as an initiator, and pioglitazone, as a template molecule were employed to preparation of non-covalent MIP adsorbent polymer, with selective operation. Based on the results obtained in this work, MIP-IMS system can be used as a powerful technique for separation, pre-concentration, and detection of Pioglitazone drug in cow serum samples. The method is exhaustively validated in terms of sensitivity, selectivity, recovery, reproducibility, and column capacity. The linear dynamic ranges of 0.10-20.00 µg/mL and 0.02-2.00 ?g/ml were obtained for the determination of Pioglitazone with positive and negative modes of IMS, respectively. The recovery of analyzed drug was calculated to be above 88% and the relative standard deviation (RSD) was lower than 6% for all experiments. Various real samples were analyzed with the coupled techniques, and the results obtained revealed the efficient clean-up of the samples using MIP separation before the analysis by IMS as a detection technique.
