Temperature-induced dispersive solid-phase extraction as a new approach for preconcentration of Sudan dyes in water and food samples prior to the determination by high-performance liquid chromatography.

This study introduced a new microextraction method named temperature-induced dispersive solid-phase extraction. The performance of the method was demonstrated with the determination of Sudan dyes in food and natural water samples. In this method, a low quantity of sorbent was added to the aqueous solution and the mixture was shaken manually for about one minute. Then, the solution was heated in an ultrasonic water bath, and the sorbent was dissolved. Subsequently, the solution was cooled down with ice water, and consequently, the solubility of the sorbent was reduced in the sample solution and became cloudy. The phase separation was accelerated by centrifugation. The upper liquid phase was picked up using a syringe, and the remainder was solved in methanol and introduced into the HPLC for analysis. Various parameters affecting the extraction yield were evaluated. Analytical parameters, including limits of detection (0.011-0.016 µg/L) and quantification (0.038-0.055 µg/L), relative standard deviations (2.3%-3.1%), and preconcentration factor (40) proved the high efficiency of the developed method for the analysis of Sudan dyes. The proposed method was used to measure Sudan dyes in water and food samples and showed good extraction recoveries (95.0%-103.5%).

Application of response surface modeling optimization in UV spectrophotometric determination of 4-aminobenzoic acid by molecularly imprinted polypyrrole.

Selective determination of 4-aminobenzoic acid (ABA) in pharmaceutical and human serum samples was performed by molecularly imprinted polypyrrole and ultraviolet (UV) spectrophotometry, based on precipitation polymerization. The molecularly imprinted polymer (MIP) was prepared using pyrrole functional monomer and ABA template molecules. The significant factors controlling the performance of the synthesized ABAMIP sorbent were screened and optimized using Plackett- Burman design (PBD) and central composite design (CCD), respectively. The model was used to obtain the optimal values of the significant response factors. The predicted MIP to NIP response ratio demonstrated an approximate deviation of 5 % from the experimental value. Under the obtained optimal conditions, the calibration curve showed a linear range of 0.05-2 mM with a correlation coefficient (r2) of 0.9920 and a limit of detection (LOD) of 0.0310 mM. The method recovery for the analyte was obtained 88.10-100.5 in the investigated real samples. The proposed ABA-MIP sorbent showed an acceptable selectivity in the presence of some pharmaceuticals.

Application of gas flow headspace liquid phase micro extraction coupled with gas chromatography-mass spectrometry for determination of 4-methylimidazole in food samples employing experimental design optimization.

BACKGROUND: 4-Methylimidazole (4-MeI) or 4-methyl-1H-imidazole, a slightly yellowish solid with molecular formula C4H6N2, is a heterocyclic compound which supposedly does not exist as a natural product and is formed when carbohydrates are heating with ammonium compounds. This compound is used in pharmaceuticals, agriculture and photography chemicals, dyes and pigments, and rubber manufacturing. In the present study, a simple and efficient sample preparation method designated gas flow headspace liquid phase microextraction (GF-HS-SDME) was employed for the extraction and preconcentration of 4-methylimidazole (4-MeI) from food and beverage samples, before its determination by gas chromatography-mass spectrometry. RESULT: To investigate the optimal conditions for the extraction process in GF-HS-SDME method, factors affecting extraction, including selection of extraction solvent, vial volume, extraction solvent ratio, position of extracting solvent, drop volume, sample volume, stirring speed, temperature, extraction time, sample pH, ionic strength of the sample solution and gas flow rate were optimized by utilizing both one-variable-at-a-time method and Plackett-Burman design. The investigation of protocol was carried out by using a standard solution containing 100.0 µg L-1 of 4-MeI in deionized water. CONCLUSION: In this study, a simple and green analytical method based on GF-HS-SDME was proposed for the extraction and preconcentration of 4-MeI from foodstuffs, followed by GC-MS determination. The main advantage of this method is its high preconcentration factor and fastness due to the application of an inert gas stream during microextraction.

Melamine Recognition: Molecularly Imprinted Polymer for Selective and Sensitive Determination of Melamine in Food Samples.

In this study, a sensitive and selective sensor is constructed to measure the melamine (MEL) using molecular imprinting polymer (MIP) technique. Chemical and electrochemical techniques are used to construct the MIP and quantitative measurements. The constructed sensor was modified with GO-Fe3O4@SiO2 nanocomposite. Screening and optimization of factors are done using statistical methods, including Plackett-Burman design (PBD) and central composite design (CCD). Under the optimized conditions, an MIP sensor showed a linear range from 5.0 × 10-7 to 1.0 × 10-5 M MEL concentration with a correlation coefficient (R 2) of 0.9997. The limit of detection was obtained (0.028 µM) with a highly reproducible response (RSD 2.15%, n = 4). The electrochemical sensor showed good results for the determination of MEL in food samples.

Selective determination of closantel by artificial neural network-genetic algorithm optimized molecularly imprinted polypyrrole using UV-visible spectrophotometry.

A molecularly imprinted polymer (MIP) for the selective solid-phase extraction (SPE) was prepared applying polymerization of pyrrole monomer in the presence of closantel (CLS) as a template molecule. The quantitative measurements were carried out using UV-Vis spectrophotometry. Several important parameters control the performance of polypyrrole sorbent. The influence of seven factors including loading time, polymerization time, amount of sorbent, stirring rate, desorption time, initiator concentration and monomer to template ratio were investigated. The optimization of parameters was performed using Plackett-Burman design (PBD), central composite design (CCD), artificial neural network (ANN) and genetic algorithm (GA). The Pareto plot showed that the effects of loading time, reaction time and amount of sorbent are most important to the process. These significant factors were investigated using CCD and the obtained data were used to train the ANN. The predicted model obtained from the trained ANN was introduced to GA as the fitness function to be optimized. The calibration curve demonstrated linearity over a concentration range of 0.010-10 mM with a correlation coefficient (R2) of 0.9833 under optimal condition. The synthesized MIP sorbent showed a good selectivity and sensitivity toward CLS. The limit of detection (LOD) for CLS was obtained 1.0 µM. The real sample analysis was performed to determine CLS in pharmaceutical and human serum samples.

A new molecularly imprinted polymer for selective extraction and pre-concentration of guaifenesin in different samples: Adsorption studies and kinetic modeling.

This paper describes the synthesis of a molecularly imprinted polymer by chemical oxidation of pyrrole as the functional monomer, and at the presence of guaifenesin as the template. The prepared polymer was used as adsorbent in molecularly imprinted solid-phase extraction followed by spectrophotometric determination. Different parameters in the solid-phase extraction including sample pH, adsorbent weight, washing solution, and elution solvent were studied to determine optimum conditions for isolation and enrichment of guaifenesin. The results showed guaifenesin was quantitatively adsorbed on the molecularly imprinted polymer at pH 6.0 and completely eluted with an ethanol-water solution (50% v/v). An enrichment factor of four with satisfactory recoveries (87.0-95.0%) was obtained. The solid-phase extraction columns could be used for up to six consecutive elution-loading cycles without significant decreases in the analyte recoveries. The method had a dynamic range of 3.0 × 10-6 -1.5 × 10-4  mol/L with a limit of detection and limit of quantification of 1.4×10-6 and 4.5×10-6  mol/L, respectively. The proposed procedure was used for the extraction and determination of guaifenesin in different pharmaceutical formulations, with satisfying results being achieved.

Method development for simultaneous determination of active ingredients in cough and cold pharmaceuticals by high performance liquid chromatography.

A rapid, simple and efficient liquid chromatographic method was developed for simultaneous determination of three active ingredients namely, chlorpheniramine maleate, phenylephrine hydrochloride and guaifenesin along with sodium benzoate preservative common cold medications (syrups) and the method was validated based on the International Conference on Harmonization (ICH) and United State Pharmacopeia (USP) guidelines. Separation of the analytes was achieved within 15 min on a nucleosil gravity phenyl column in a single run with a mobile phase consisting of methanol: buffer mixture (15:85 v/v) at room temperature, in isocratic mode with flow rate of 0.8 mL min-1. A comprehensive study on specificity, range, accuracy (recovery), intraday and interday precisions, limit of detection, limit of quantitation, robustness, ruggedness, system suitability and specification was performed as a part of method validation. The linearity was obtained in the range of 7.1-12.2 µg mL-1 (r2 = 0.9984), 17.6-30.1 µg mL-1 (r2 = 0.9995), 39.6-67.8 µg mL-1 (r2 = 0.9995) and 351.1-601.8 µg mL-1 (r2 = 0.9996) for chlorpheniramine maleate, phenylephrine hydrochloride, sodium benzoate and guaifenesin, respectively. The proposed liquid chromatographic method was successfully applied for the routine analysis of these compounds in different commercial cough and cold pharmaceutical preparations including syrups with no interference from the excipients.

Nanogram/mL detection of nortriptyline: Preparation of a molecularly imprinted polymer for spectrophotometric determination of nortriptyline based on multivariate optimization methods.

In this work, the molecularly imprinted polymer was used as a selective sorbent in solid-phase extraction method for the spectrophotometric determination of nortriptyline at 239 nm. Molecularly imprinted polymer was synthesized by pyrrole as a functional monomer in the presence of nortriptyline as a template. Several factors, consist of the concentration of the monomer to template ratio, amount of initiator, stirring rate, reaction time, the pH of the buffer solution, amount of sorbent, loading time, shaking rate of loading, extraction time, and shaking rate of extraction were evaluated due to their effectiveness in the preparation and extraction capability of molecularly imprinted polymer. Multivariate optimization methods, such as Plackett-Burman and central composite designs, were employed to find and optimize the significant factors. Under the selected optimal conditions, molecularly imprinted polymer showed a linear range from 0.1 to 100 µmol/L (0.026 to 26 µg/mL) nortriptyline, a detection limit of 10.3 nmol/L (2.7 ng/mL), a highly repeatable (relative standard deviation of 3.7%) and reproducible response (relative standard deviation of 4.6%), and a good selectivity in the presence of structurally related molecules. Furthermore, molecularly imprinted polymer showed high extraction efficiency and was successfully used for the determination of nortriptyline in real samples.

Screen printed carbon electrode sensor with thiol graphene quantum dots and gold nanoparticles for voltammetric determination of solatol.

This work, a highly selective and sensitive sensor is described for voltammetric determination of the sotalol (SOT). The dual actions of sotalol lead to reductions in the automaticity of myocardial cells and in conduction through the atrioventricular node. Drug analysis has an extensive impact on public health. The molecularly imprinted sensor was constructed by modifying a screen printed carbon electrode (SPCE) with thiol graphene quantum dots (GQD-SH) and gold nanoparticles (AuNPs). Under optimal conditions the nanotools has a dynamic range that covers the 0.1-250 µM SOT concentration range, and the detection limit is 0.035 µM. This is lower than any of the previously reported methods. The MIP-sensor also exhibited excellent selectivity, good stability and adequate reproducibility for the detection of the SOT over its structural analogs. The prepared sensor was successfully applied to the measurement of SOT in various real samples including tablet and human blood serum.

Multivariate optimization of mebeverine analysis using molecularly imprinted polymer electrochemical sensor based on silver nanoparticles.

Thin film of a moleculary imprinted polymer (MIP) based on electropolymerization method with sensitive and selective binding sites for mebeverine (MEB) was developed. This film was cast on pencil graphite electrode (PGE) by electrochemical polymerization in solution of pyrrole (PY) and template MEB via cyclic voltammetry scans and further electrodeposition of silver nanoparticles (AgNPs). Several parameters controlling the performance of the silver nano particles MIP pencil graphite electrode (AgNPs-MIP-PGE) including concentration of PY(mM) concentration of mebeverine (mM), number of cycles in electropolymerization, scan rate of CV process (mV. s-1), deposition time of AgNPs on to the MIP surface (s), stirring rate of loading solution (rpm), electrode loading time (min), pH of Britton-Robinson Buffer (BRB) solution were examined and optimized using multivariate optimization methods such as Plackett-Burman design (PBD) and central composite design (CCD). Two dynamic linear ranges of concentration for the MIP sensor were obtained as. 1 × 10 -8 to 1 × 10 -6 and 1 × 10 -5 to1 × 10-3 M with the limit of detection (LOD) of 8.6 × 10 -9M (S/N = 3). The proposed method was successfully intended for the determination of MEB in real samples (serum, capsule). The sensor was showed highly reproducible response (RSD 1.1%) to MEB concentration.

An electrochemical chlorpyrifos aptasensor based on the use of a glassy carbon electrode modified with an electropolymerized aptamer-imprinted polymer and gold nanorods.

A highly selective and sensitive aptasensor is described for voltammetric determination of the pesticide chlorpyrifos (CPS). The sensor was constructed by modifying a glassy carbon electrode (GCE) with gold nanorods and a polymer that was molecularly imprinted with an aptamer against CPS. This results in double specific recognition. Under optimal conditions and a working potential as low as 0.22 V (vs. Ag/AgCl), the nanotools has a dynamic range that covers the 1.0 fM - 0.4 pM CPS concentration range, and the detection limit is 0.35 fM. This is lower than any of the previously reported methods. This MIP-aptasensor is selective over structural analogs, stable, and adequately reproducible. It was successfully applied to the determination of CPS in spiked food samples. Graphical abstract Impedimetric detection of Chlorpyrifos by using a Fe(CN)63-/4- probe based on double recognition of aptamer-molecular imprinted polymer onto a glassy carbon electrode modified with gold nanorod nanocomposite. The incubation with Chlorpyrifos lead to an increase of electron transfer resistance.

A novel electrochemical sensor based on electrode modified with gold nanoparticles and molecularly imprinted polymer for rapid determination of trazosin.

A novel molecularly imprinted polymer sensor for fast and direct determination of trazosine (TR) was studied. The voltammetric sensor based on molecularly imprinted polymer (MIP) with disposable gold nanoparticles modified screen printed carbon electrode (MIP/AuNPs/SPCE) is developed for the determination of TR. Under the optimum conditions, the peak current of the sensor and TR concentration showed a good linear relationship over the range from 2.0 to 250.0 µM, with a low detection limit (S/N = 3) of 0.3 µM. The modified electrode demonstrated good electrocatalytic properties toward the oxidation of TR. This sensor selectively detected TR even in the presence of high concentration of similar compounds and MIP/AuNPs/SPCE was also confirmed successfully for the determination of TR in the various real samples including human blood serum, urine and trazosin tablet.

Determination of methimazole based on electropolymerized-molecularly imprinted polypyrrole modified pencil graphite sensor.

Preparation of a molecularly imprinted polymer (MIP) film and its recognition property for methimazole (MMZ) was investigated. The polypyrrole (PPy) film was prepared by the cyclic voltammetric deposition of pyrrole in the presence of a supporting electrolyte (NaClO4·H2O) with and without MMZ through on a pencil graphite electrode (PGE). A computational study based on density functional theory was developed to evaluate the template-monomer geometry and interaction energy in the prepolymerization mixture. The performance of MIP sensor and non-imprinted polymer (NIP) film was evaluated by differential pulse voltammetry (DPV). The most important parameters controlling the performance of sensor were investigated and optimized. The prepared electrode was used for MMZ measurement by a three-step procedure, including analyte extraction in the electrode, electrode washing and electrochemical measurement of MMZ. The molecularly imprinted film exhibited a high selectivity and sensitivity toward methimazole in the experimental conditions. The calibration curve demonstrated linearity over a concentration range of 0.007-6mM with a correlation coefficient (r2) of 0.9808. The accuracy of the method was studied through spiking blank samples showed recovery of 98% with precision of 4%. Limit of detection based on S/N=3 was obtained 3×10-6M. The proposed sensor was applied successfully to determine MMZ in biological model samples and pharmaceuticals.

Spectrophotometric determination of fluoxetine by molecularly imprinted polypyrrole and optimization by experimental design, artificial neural network and genetic algorithm.

A selective method based on molecularly imprinted polymer (MIP) solid-phase extraction (SPE) using UV-Vis spectrophotometry as a detection technique was developed for the determination of fluoxetine (FLU) in pharmaceutical and human serum samples. The MIPs were synthesized using pyrrole as a functional monomer in the presence of FLU as a template molecule. The factors that affecting the preparation and extraction ability of MIP such as amount of sorbent, initiator concentration, the amount of monomer to template ratio, uptake shaking rate, uptake time, washing buffer pH, take shaking rate, Taking time and polymerization time were considered for optimization. First a Plackett-Burman design (PBD) consists of 12 randomized runs were applied to determine the influence of each factor. The other optimization processes were performed using central composite design (CCD), artificial neural network (ANN) and genetic algorithm (GA). At optimal condition the calibration curve showed linearity over a concentration range of 10-7-10-8M with a correlation coefficient (R2) of 0.9970. The limit of detection (LOD) for FLU was obtained 6.56×10-9M. The repeatability of the method was obtained 1.61%. The synthesized MIP sorbent showed a good selectivity and sensitivity toward FLU. The MIP/SPE method was used for the determination of FLU in pharmaceutical, serum and plasma samples, successfully.

Bioactive sesquiterpene lactone from Artemisia santolina / Lactona sesquiterpénica bioactiva de Artemisia santolina

Most species of genus Artemisia L. (Compositae) are medicinal herbswith several uses in the folk medicine worldwide. In the present study, methanol extract of Artemisia santolina has been subjected for isolation of its metabolites along with evaluation of cytotoxic activity against Artemia salina larvae. The structures of the compounds determined by 1H-and 13C-NMR, HMQC, HMBC, 1H-1H COSY and Mass spectral analysis. Two sesquiterpenes, 1,5-dihydroxy- 4(15)eudesman-12,6-olid (artemin) (1), 2-hidroxy-2,6,10-trimethyl-7,10- oxide-3,11-dodecadien-5-one (2) and one flavonoid, 5,7,4'-trihydroxy-6,3'-dimethoxyflavone (jaceosidin) (3) have been successfully characterized. Cytotoxicity of the sesquiterpene lactone (1), was assessed on Artemia salina larvae and resulted in IC50 value of 6.44 µg/mL, which was more potent compared to the positive standard berberine hydrochloride (IC50 = 26 µg/mL). In this study, the separation and identification of two sesquiterpenes and one flavone from the aerial parts of A. santolina is described. Among them the compound artemin (1) showed a toxicity effect against A. salina nauplii.

La mayoría de las especies del género Artemisia L. (Compositae) son hierbas medicinales con varios usos en la medicina popular en todo el mundo. En el presente estudio, el extracto metanólico de Artemisia santolina ha sido sometido al aislamiento de sus metabolitos junto con la evaluación de la actividad citotóxica contra las larvas de Artemia salina. Las estructuras de los compuestos se determinaron mediante RMN 1H y 13C, HMQC, HMBC, 1H-1H COZY y análisis espectral de masas. Dos sesquiterpenos, 1,5-dihidroxi-4 (15) eudesman- 12,6-olid (artemin) (1), 2-hidroxi-2,6,10-trimetil-7,10-óxido-3,11-dodecadien-5-ona (2) y un flavonoide, 5,7,4'-trihidroxi-6,3'- dimetoxiflavona (jaceosidina) (3). Se evaluó la citotoxicidad de la lactona sesquiterpénica (1) en larvas de Artemia salina y resultó en un valor de CI50 de 6,44 µg/ml, que era más potente en comparación con el clorhidrato de berberina estándar positivo (CI50 = 26 µg/ml). En este estudio se describe la separación e identificación de dos sesquiterpenos y una flavona de las partes aéreas de A. santolina. Entre ellos, el compuesto artemin (1) mostró un efecto de toxicidad contra los nauplios de A. salina.

Mechanistic study of in vitro chemical interaction of trimipramine drug with barbituric derivative after its oxidation: Electrochemical synthesis of new dibenzazepine derivative.

Electrochemical oxidation of trimipramine in the absence and presence of 1,3 dimethyl barbituric acid as a nucleophile in aqueous solution has been studied using cyclic voltammetry and controlled-potential coulometry electrolysis. Voltammetric studies of electro-oxidation of trimipramine were realized in a range of pH1.0 to 8.0 in the absence and presence of 1,3 dimethyl barbituric acid. Based on the obtained electrochemical results, dimerization is the main reaction of electro-oxidation of trimipramine in the absence of nucleophile. The voltammetric data indicate that the 1,3 dimethyl barbituric acid participation in Michael addition reaction with the oxidized dimeric form of trimipramine via an ECEC electrochemical mechanisms. On the other hand the results indicate existence of a catalytic (EC') electrochemical mechanism in parallel with ECEC electrochemical mechanism. This method provides a facile and one-pot procedure for the synthesis of new dibenzazepine derivative. Finally, a possible mechanism is proposed for the electrode process, on the basis of the present and previous investigations. The product has been characterized by IR, 1H NMR, 13CNMR and MS methods.

An innovative method for analysis of Pb (II) in rice, milk and water samples based on TiO2 reinforced caprylic acid hollow fiber solid/liquid phase microextraction.

In the present study, nano-sized titanium oxides were applied for preconcentration and determination of Pb(II) in aqueous samples using hollow fiber based solid-liquid phase microextraction (HF-SLPME) combined with flame atomic absorption spectrometry (FAAS). In this work, the nanoparticles dispersed in caprylic acid as an extraction solvent was placed into a polypropylene porous hollow fiber segment supported by capillary forces and sonification. This membrane was in direct contact with solutions containing Pb (II). The effect of experimental conditions on the extraction, such as pH, stirring rate, sample volume, and extraction time were optimized. Under the optimal conditions, the performance of the proposed method was investigated for the determination of Pb (II) in food and water samples. The method was linear in the range of 0.6-3000µgmL-1. The relative standard deviations and relative recovery of Pb (II) was 4.9% and 99.3%, respectively (n=5).

Development of novel electrochemical sensor on the base of molecular imprinted polymer decorated on SiC nanoparticles modified glassy carbon electrode for selective determination of loratadine.

A novel and selective electrochemical sensor was successfully developed for the determination of loratadine by drop coating of synthesized loratadine molecularly imprinted polymers on the surface of glassy carbon electrode modified with silicon carbide nanoparticles. The performance of the constructed sensor was evaluated by cyclic voltammetry, scanning electron microscopy, and electrochemical impedance spectroscopy techniques. Under optimized conditions, the resulting calibration curve exhibited a linear response within a concentration range of 1-33µM with a low detection limit (S/N=3) of 0.15µM. Finally, the proposed method was successfully applied as a selective, stabile, sensitive, simple, reproducibility electrochemical sensor with good repeatability for the determination of loratadine in real samples and satisfactory results were obtained.

Magnetically responsive polycaprolactone nanoparticles for progesterone screening in biological and environmental samples using gas chromatography.

A new Fe3O4/poly(є-caprolactone) (PCL) magnetite nanocomposite was fabricated and used as a sorbent for magnetically mediated PCL microspheres solid-phase extraction (MM-PCL-SPE) followed by gas chromatography-flame ionization detection (GC-FID) for monitoring of progesterone (PGN) hormone in biological and environmental matrices, namely blood serum, tap water, urine, and hospital wastewater. The nanomagnetite core of the sorbent was synthesized by a co-precipitation method. Magnetic nanoparticles (MNPs) were then microencapsulated with PCL microspheres using emulsion polymerization. The nanocomposite was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The magnetite sorbent can be effectively dispersed in aqueous solution and attracted to an external magnetic field. The MM-PCL-SPE process for PGN assay involved (a) dispersion of the sorbent in the donor phase aqueous solution with sonication, (b) exposure to a magnetic field to collect sorbent that had adsorbed the analyte, and (c) solvent desorption of extracted PGN for GC-FID analysis. The work demonstrates the usefulness of MM-PCL-SPE in the rapid and sensitive monitoring of trace amounts of PGN in real samples. The limit of detection (LOD) and limit of quantification (LOQ) were 1.00 and 3.30 ng/mL, respectively. The relative recoveries in real samples were adequate. Linearity was observed over a wide range of 2.2-10,000.0 ng/mL in aqueous media and urine and 0.01-70.0 µg/mL in blood serum. Graphical Abstract In this research new Fe3O4/poly(є-caprolactone) (PCL) magnetite microspheres were developed as an efficient sorbent for solid-phase extraction of progesterone hormone in biological and environmental matrices.

Computational design and multivariate optimization of an electrochemical metoprolol sensor based on molecular imprinting in combination with carbon nanotubes.

This work describes the development of an electrochemical sensor based on a new molecularly imprinted polymer for detection of metoprolol (MTP) at ultra-trace level. The polypyrrole (PPy) was electrochemically synthesized on the tip of a pencil graphite electrode (PGE) which modified whit functionalized multi-walled carbon nanotubes (MWCNTs). The fabrication process of the sensor was characterized by cyclic voltammetry (CV) and the measurement process was carried out by differential pulse voltammetry (DPV). A computational approach was used to screening functional monomers and polymerization solvent for rational design of molecularly imprinted polymer (MIP). Based on computational results, pyrrole and water were selected as functional monomer and polymerization solvent, respectively. Several significant parameters controlling the performance of the MIP sensor were examined and optimized using multivariate optimization methods such as Plackett-Burman design (PBD) and central composite design (CCD). Under the selected optimal conditions, MIP sensor was showed a linear range from 0.06 to 490 µmol L(-1) MTP, a limit of detection of 2.88 nmol L(-1), a highly reproducible response (RSD 3.9%) and a good selectivity in the presence of structurally related molecules. Furthermore, the applicability of the method was successfully tested with determination of MTP in real samples (tablet, and serum).