Vol.:(0123456789) 1 3 Journal of the Iranian Chemical Society https://doi.org/10.1007/s13738-018-1551-4 ORIGINAL PAPER Molecularly imprinted based solid phase microextraction method for monitoring valproic acid in human serum and pharmaceutical formulations Razieh Zakerian 1  · Soleiman Bahar 1 Received: 8 June 2018 / Accepted: 9 November 2018 © Iranian Chemical Society 2018 Abstract In this paper, a straightforward method is presented to detect valproic acid after its microextraction. Molecularly imprinted polymer fber was used in conjunction with chromatography-fame ionization to achieve this goal. A narrow bore silica capillary was adopted as a mold, via the copolymerization of meth acrylic acid–ethylene glycol dimethacrylate imprinted with VPA, to synthesize the fber. Extraction temperature, extraction time, salt addition, pH, stirring rate, and desorption temperature—all of which are factors that can infuence the extraction process—were measured, and adjusted accordingly. Linearity, precision, and detection limits, as analytical elements, were also evaluated under optimum conditions. Readings showed a linear range of 0.03–100 µg L − 1 (r 2 = 0.998), and the limit of detection was measured as 0.01 µg L − 1 . The estab- lished method was then applied in selective detection of valproic acid in tablet, syrup and human serum samples successfully. Keywords Sample preparation · Gas chromatography · Serum sample · Flame ionization detector Introduction Analytic tests have always been important in quality control and continued development of pharmaceutical products. Furthermore, each drug may have its own therapeutic, as well as toxic efects which need to be observed in various biological fuids. The same fuids are also commonly used in pharmacokinetic studies. Valproic acid (VPA, 2-propylpen- tanoic acid), an eight-carbon, branched-chain fatty acid, is one such fuid, which is especially suitable for these tests and studies due to its anticonvulsant properties, which make it relatively free of undesirable side efects on the central nervous system. It is also a common treatment for seizures, and is widely used as a stabilizing agent in a number of psychiatric disorders [1]. VPA levels need to be monitored in a patient’s serum or plasma as changes in VPA dose, concomitant medications, or patient’s clinical condition occur [2]. Various methods have been reported in the feld’s literature for this purpose. Gas chromatography [3–5], liquid chromatography [6–8] and capillary electrophoresis [9–11] are the main documented methods used to determine levels of VPA. Although HPLC methods are frequently applied for this analysis, due to volatile nature of VPA, GC is often pre- ferred, ofering an unrivaled high resolution [12]. The bio- analytical component of a pharmacokinetic study requires sample treatments such as extraction, pre-concentration and clean-up steps to improve sensitivity and selectivity. Solid phase microextraction (SPME), introduced in the 1990s by Pawliszyn and his peers, which meets the green analytical chemistry standards, is one of the most widely used techniques in the sample preparation process [13]. It has been a widely used approach in an expansive array of felds, among which are environmental, alimentary, forensic, clinical, pharmaceutical, and biological studies, because it is simple to conduct, easy to automate, pairs up with chro- matographic instruments in an ofhand manner, and is sol- vent-free [14–19]. The extraction efciency of an SPME technique, when it comes to its sensitivity, selectivity, and reproducibility, is dependent on the characteristics of the sorbent-coated on the fber, and the properties of the targeted analytes. Diferent sorts of sorbent-coated SPME fbers have Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13738-018-1551-4) contains supplementary material, which is available to authorized users. * Razieh Zakerian Razieh_Zakerian@yahoo.com 1 Department of Chemistry, Faculty of Science, University of Kurdistan, P.O. Box 416, Sanandaj, Iran