Conseguences of soil crude oil pollution on some wood properties of olive trees Chemistry |44 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Synthesis, Characterization of Chlropheniramine maleate– Molecularly Imprinted Polymers and Their Application as Sensors for the Determination of the Drug in Some Pharmaceutical Preparations Marwa Raad Dept. of Chemistry/ College of Education/ University of Samarra Khalaf Farris Alsamarrai Dept. of Chemistry/College of Education/ University of Samarra Yehya Kamal Al-Bayati Dept. of Chemistry/ College of Science/ University of Baghdad Email: biochemistry348@gmail.com Received in:2/November/2016,Accepted in:2/November/2016 Abstract New chlropheniramine maleate (CPM) selective electrochemical membranes were prepared by using chlropheniramine maleate -molecularly imprinted polymers. MIP was prepared by bulk polymerization using 2-hydroxyethyl methacrylate (2-HEMA) as monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker and a benzoyl peroxide (BPO) as an initiator at 60 0 C. Three CPM-MIP electrodes were constructed by using tri-tolyl Phosphate (ToCP), tris (2- ethyl hexyl) Phosphate (TEHP) and tributyl Phosphate (TBP) as plasticizers in PVC matrix.Electrode parameters including slopes, working concentrations ph. The interference effect in the presence of (Na + , Mg +2 , Al +3 , Glycine, Alanine, Arginine and Phenylalanine) was studied using the separated and mixed methods to determine the selectivity coefficient determination. NIP prepared by using the same composition of MIP molecularly imprinted polymer electrodes except the template (CPM). The slopes of CMP- MIP are 21.00, 21.50 and 19.08 mV/ decade, linearity range for the electrodes around. (10 -5 - 10 -1 ) M, the stable at a pH range from 4.0 to 8.5 and lifetime ranged from 30 to 10 days. The suggested electrodes were successfully applied for the determine of CPM in some pharmaceutical preparations, which were given acceptable accuracy. Keywords: Molecularly Imprinted Polymers, Chlorpheniramine maleate, Different plasticizers, Pharmaceutical samples mailto:biochemistry348@gmail.com Chemistry |45 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Introduction Chlorpheniramine maleate (CPM), 3-(p-chlorophenyl)- 3-(2-pyridyl)-N,N-dimethyl propyl amine (C16H19ClN2, C4H4O4), is a powerful first-generation alkylamine anti- histamine, H1- receptor antagonist, widespread used for relive symptoms of joint cold and allergies rhinitis, with weakness soothing property, the structure is shown in Figure(1). Chlorpheniramine was used to relieve symptoms of allergies reactions, hay fever, rhinitis, urticarial, and asthma. Its done used in veterinary medicine. One of the most commonly used of the classical antihistaminic, it habit causes less drowsiness and anesthesia than promethazine. Chlorpheniramine is a histamine H1 antagonist of the alkyl amine class. Competing with histamine for the normal H1-receptor places on effector cells of the digestive system, vascular and respiratory system [1, 2]. Many analytical methods are described for determination of Chlorpheniramine maleate in pharmaceuticals such as spectrophotometric methods and derivative spectrophotometric [3- 6], gas chromatography and liquid chromatography with ion pair reagents [7- 10]. Chlorpheniramine maleate tablets made by Manfei et al. and used as samples for analysis using near infrared chemical imaging to acquire the concentration information of CPM coupled with partial least squares for quantitative analysis of CPM [11]. Molecular imprinted polymers (MIPs) exhibiting high selectivity to the template molecules and used for chemical analysis. MIP is formed by polymerization of the template and the functional monomers. Few papers were published of chlropheniramine maleate molecularly imprinted polymers, such as chlropheniramine- imprinted polymer which was prepared by Chen at al. [12] used for solid phase extraction and used for separation of chlorpheniramine from diphenhydramine. MIP for d-chlorpheniramine has been prepared by Jun and chino [13] and using methacrylic acid and ethylene glycol dimethacrylate as a functional monomer and cross-linker. MIP showed the highest recognition for chlropheniramine and slight recognition for its structurally related compounds. Preparation of spherical MIP is described by Walsh et al. [14] with chlropheniramine and other antihistamine drugs and studied the physical properties of the polymers. Recent MIP was reviewed by Jesika et al. [15] including the previous and current literature regarding the analytical tools employed for synthesized MIPs. The review was about bio-macro molecules such as antibodies and enzymes. Recently several papers were published in electrochemical by preparing electrodes based on MIP for drug determination. MIP and NIP were constructed by Al-Mustafa et al. [16] using dextromethorphan as a template and used for determination of CPM in cough syrups. Abu-Dalo et al. [17] prepared a new electrochemical sensor using copper-carboxyl benzotrizole complex based on copper ion imprinted polymer with carboxyl benzotrizol as a new ligand, the electrodes used for determination of copper ions in wastewater samples. Several molecular imprinted polymer membranes of azithromycin constructed by Abu-Dalo et al. [18] using graphite electrode, the Azin-MIP was prepared by thermal polymerization and the electrodes were used for the determination of azithromycin in commercial tablets and capsules. Al-Bayati [19] prepared ibuprofen MIP using methacrylic acid as monomer with different plasticizers and determined ibuprofen in pharmaceutical samples. Graphite electrodes coated with membranes based on risperidone imprinted polymer used for determination of risperidone in pharmaceutical formulations [20]. In this study the chlorpheniramine maleate imprinted polymer sensors were prepared using different plasticizers in PVC matrix by polymerization with 2- hydroxyethyl methacrylate as a monomer. The electrode parameters were studied and applied for the determination of CMP in pharmaceutical samples. Chemistry |46 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Experimental Apparatus Expansible ion analyst sample WTW from Germany, pH meter WTW model pH 720, Germany and a saturated calomel electrode type Gallenkamp, USA were used in this work. All potentiometric measurements were made at room temperature. The performance of the electrodes were investigated by measuring the potential of CPM solutions with concentrations ranged from10 -6 to 10 -1 M. Each solution was stirred and the potential was recorded at equilibrium. The calibration curves were obtained by plotting the response against logarithmic function of Chlorpheniramine maleate concentration. Construction of the electrode body and immobilization of CPM-MIP in PVC matrix membrane it was conducted use the method given by Craggs et al [21]. Reagents and standard solutions 1. All chemical reagents used were with the highest purity, 2-hydroxy ethyl methacrylate (2-HEMA), benzoyl peroxide (98%), ethylene glycol dimethacrylate (EGDMA) (98%). Plasticizer, tri- tolyl phosphate (ToCP), tris (2-ethyl hexyl) phosphate (TEHP) and tri butyl phosphate (TBP) were obtained from Fluka AG. Other chemicals and reagents of analytical grade quality were obtained from Fluka, BDH and Aldrich. The values of viscosity and dielectric constant are listed in Table (2). 2. chlorpheniramine maleate standard was a gift from the State Company of Drug Industries and Medical Appliances (SDI- Iraq). Panadol tablets (Australia) and Tylolhot tablet of 4 mg chlorpheniramine maleate (Turkey) were obtained from local pharmacies. 3. The stock Standard solution of 0.1 M chlorpheniramine maleate it has been prepare by dissolve 3.908g of standard Chlorpheniramine maleate in ethanol and diluted to 100 mL; standard solutions ranging of 10 -6 -10 -1 M it has been freshly prepared from the stock solution. 4. 0.1M stock solution of each of interfering species; NaCl, MgCl2, Al(NO3)3.9H2O, glycine, alanine, arginine and phenylalanine were prepared. Synthesis of Imprinted Polymer In glass test tube 50 mL , 8.2449 mmol (1.0730 gm) of the monomer (2-HEMA), 14.00 mmol(2.7750 gm) of the cross-linker (EGDMA), 0.7258 mmol (0.2837gm) of drug as template, 0.1238 mmol (0.030gm) of initiator (BPO) and 5 mL of chloroform were mixed in a good way even dissolve all components. The solution was degased for 30 minutes with nitrogen gas and cured at 60 0 C for 30 minutes. The polymer was leave for 24 hours to dry and after that was crushed and washed with (1:9) (methanol: acetonitrile) to eject template and washed repeatedly to make sure every drug was ejected the polymer and dried at 60 0 C for 24 hours. The polymer was ground and sifted by mortar the particles with size less than 100 μm was collection and used in preparation sensing. The non-imprinted polymer (NIP) it has been prepared using the same method but without drug (Template). Synthesis of Membrane and Electrode The PVC membrane it has been prepared by mixing 0.1700 gm PVC, 0.4000 gmToCP, TEHP and TBP as plasticizers and 0.0200 gm of the MIP. This mixture it has been resolved in 4 mL of THF, and the mixture was poured into a (35) cm diameter glass ring and allowed to evaporate for 24 hours. Construction of the electrode was made depending to the reference [21]. Chemistry |47 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Morphological Characterization MIP according to the different types of interaction of template and functional monomer in polymerization process can be divided into covalent, non-covalent, metal ion and non-polar imprinting.[22] In this work, we will mainly focus on the one most common types, covalent imprinting, metal ion imprinting and non-covalent imprinting. Non-covalent imprinting refers to molecular imprinting strategies in which template and functional monomer form a complex in solution mainly driven by weak forces such as hydrogen bonding, electrostatic interactions, hydrophobic effects and pi-pi interaction. Non-covalent imprinting is the predominant method for imprinting due to the ease of preparation. Typically, this technique requires no or little synthetic chemistry. The imprinting process starts spontaneously when monomer and template are mixed together. The associated monomer/template complex is stable under polymerization conditions such as free radical polymerization. However, non-covalent imprinting has drawbacks Non-covalent imprinting process is a dynamic equilibration. That leads to low yield of imprinted sites. It also creates a lot of non-selective binding sites due to the heterogeneity of non-covalent imprinting process, which may largely affect the imprinting efficiency. Scanning electron microscopy (SEM) was used for primary evaluation of the MIP particles. Fig3 (a and b) shows the morphology of MIP before and after washing showed by electron microscope in figure 1. A pore on the surface (figure 3a) about 10 µm may indicate the binding sites to the polymer. Figure 3b shows clear holes about of 20 µm in sizes which may indicate a complete removal of the template from the membrane. Potential Measurements All measurements conducted out in a 50 mL double walled glass cell, with fixed magnetic stirring of the test solution at room temperature. The performance of the electrodes was investigated by measuring the potential of Chlorpheniramine maleate solutions prepared with a concentration range of (10 −6 - 10 −1 ) M by prepared serial dilution. The slope, response time, detection limit and life time were calculated from the calibration curve. The electrochemical performance of the two proposed sensors it was rated depending on the IUPAC recommendations data. Sample preparation for analysis Ten tablets of each drug formulation were weighed accurately 6.4163g and soft powdered in a small dish. An amount of powder equivalent to 0.0390g of the drug was accurately transferred to 100 mL volumetric flasks and diluted to the mark with distilled water to prepare 10 -3 M solution of Chlorpheniramine maleate. Another amount of powder equivalent to 0.0039 g transferred to 100 ml volumetric flasks and diluted to the mark with deionized distilled water to prepare 10 -4 M solution of Chlorpheniramine maleate. The probably readings production by immersing the prepared electrodes in the prepared solutions were recorded. Chemistry |48 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Results and discussion Characterization The Fourier transmission infrared spectrometry (FTIR) spectra of leached and unleached Chlorpheniramine maleate imprinted polymers MIP and CPM were recorded in the range of (400–4000) cm -1 by the KBr pellet method (table 1). The FTIR spectrum of Chlorpheniramine maleate shows a sharp peak at1701 cm -1 for carbonyl stretching of ester group when comparing with the FTIR spectrum of MIP (before template removal) which show two peaks at (1635,1724) cm -1 of ester groups and cross-linked . The FTIR spectrum of CPM and MIP(before template removal) shows sharp peak at 651 cm -1 for the substation chloride , also appearance band Out-of plane-para- substation at 864 cm -1 and show peaks at (1558,1585) cm -1 for aromatic conjugation and when compared with the FTIR spectrum of MIP( after template removal) all these peaks were disappeared. Influence of membrane composition Electrodes based on membranes of CMP-MIP and CPM-NIP in PVC matrix were prepared using chlorpheniramine maleate as a template and 2-hydroxcyethyl methacrylate as monomer and ToCP, TEHP and TBP as plasticizers. All CPM electrodes were calibrated at different concentrations of CMP solutions ranged from (10 -6 -10 -1 ) M and electrodes reach equilibrium very fast in all of these concentrations of CMP. Electrodes based on membranes (I, II and III) show good electrode parameters and the results of electrode specification are listed in Table 2. The conductivity of the PVC membrane depends on the value of dielectric constant and by increasing the dielectric constant the conductivity of PVC membrane increases. Also, the quantity and viscosity of the plasticizer influence the parameters of the electrode and the mobility of the species in the membrane. All the electrodes (I, II and III) show near-Nernistain slopes of 21.00, 21.51 and 19.08 mV/ decade with excellent detection limits as shown in Table 2, the lifetime of electrode based on ToCP plasticizer was around 30 days higher than the other plasticizers due to the high viscosity of ToCP (58.0 cSt). The electrodes were calibrated two times a week over CMP concentration ranged from 10 -1 – 10 -6 M and the slopes during this period gives response drift of ± 0.90 mv/ decade. The ratio of template 0.7258 mmole: 8.2449 mmole monomer: 14.0000 mmole cross linker: 1.600 mmole (1: 34: 57.8: 6.6) used in this study gave good results for CPM-MIP electrodes. This ratio shows non-covalent bonding and can easily remove the template from the polymer. The calibration curves of CMP electrodes were plotted on Orion 7 cycle semi log paper and their results are listed in Figure 4 . The values of detection limit were calculated using equation ΔE = 59/z [22]. Effect of pH Effect of pH on the electrochemical of CMP-MIP sensor was studied. The electrode response was measured at a fixed concentration of chlorpheniramine solution (10 -2 , 10 -3 and 10 -4 ) M at different pH values. The pH of CMP solution was adjusted by adding hydrochloric acid or sodium hydroxide solution and the response of CMP-MIP sensor is independent on pH range from 4.0 to 8.5. At pH values lower than 4.0 the CMP becomes unstable may be due to the interaction of nitrogen species of CMP with hydrogen ion forming a bond or the electrode sensor response to hydrogen ion, while at pH > 8.0 the basicity of CMP solution leads to the Chemistry |49 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 formation of non-ionic of CMP. The results of pH study are listed in Table 3 and a plot of electrode based on ToCP plasticizer at three concentrations of CMP is shown in Fig. 5. Interference studies The selectivity coefficients of some inorganic cations and species (Na + , Mg +2 , Al +3 , glycine, alanine, arginine and phenylalanine) were determined by using separate solution method (SSM). The potential was measured for two solutions, one containing chlorpheniramine maleate and the other contains the interfering species and using the equation 1 [23] for calculating the selectivity coefficient. Log Kpot= [(EB − EA)/(2.303RT/zF)]+ (1 − zA/zB) log aA……….(1) EA, EB; zA, zB; and aA, are the potentials, charge numbers, and activities for the primary A and interfering B ions, respectively at aA= aB. The selectivity coefficients were also calculated by the using mixed solution method according to the equation 2 [24]. KpotA,B = aA/ (aB)ZA/ZB……………………..(2) The selectivity coefficients of electrodes (I, II and III) were calculated for CMP concentrations ranged from (10 -6 - 10 -1 ) M. Selectivity coefficients for the electrode based on ToCP plasticizer were listed in Table 4. The values of selectivity coefficients presented in Table 5 indicate that the interference of all species increase by decreasing the concentration of CMP solutions. The order of interference effect for cations is monovalent > divalent > trivalent. None of the species glycine, alanine, arginine and phenylalanine interferes seriously with electrode response. Fig. 6 shows the plot of log concentration with log K. Mixed solution method was also used at two fixed of concentrations of interfering species at (10 -2 and 10 -3) M using the equation 2. The results of selectivity coefficients of the species using mixed solution method are listed in Table 7. The same behavior of selectivity coefficient was obtained by the two methods. Sample analysis Standard addition and direct methods were used for determination of chlorpheniramine maleate in commercial tablets using CMP-MIP (I) electrode. Two types of pharmaceutical formulations, (Panadol) from Australia and Tylolhot from (Turkey) were used for analysis. The values of recoveries and relative standard deviations using electrodes I, II and III are listed in Table 8, 9 and 10. Good recoveries were obtained ranged from (101 – 105) % which is in good agreements with British Pharmacopoeia (BP) [25]. The relative standard deviation was ranged (0.6300 to 1.8700) Conclusion In this work chlorpheniramine maleate, imprinted polymers were prepared by using 2- hydroxy ethyl methacrylate as a monomer with different plasticizers. The good sensor was based on ToCP plasticizer and used for determination of CMP in commercial tablets, and the specification of the electrodes was studied. Chemistry |50 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 References 1.USP, United State Pharmacopoeia convention, 2002, 1263. 2.Wikipedia, http://en.wikipedia.org/wiki/chlorpheniramine maleate 3.Mohammed AktarSayeed and SohelRana, (2013), In vitro and Invivo Drug-Drug Interaction Study between Ketotifen Fumerate and Chlorpheniramine Maleate at Gastric and Intestinal pH. Int. J. of research in Pharmaceutical and Biomedical Sciences, 4(1), 227-233. 4. Ladmeera, Hasumati Raj and Vineet Jain, (2015), - a review of analytical methods for determination bromhexine hydrochloride in pharmaceutical and biological samples. Asian J. Res. Pharm. Sci., 5(2), 76-82. 5. Maryam Kazemipour and Mehdi Ansari, (2005), Gabapentin Determination in Human Plasma and Capsule by Coupling of Solid Phase Extraction, Derivatization Reaction, and UV- Vis Spectrophotometry. Iranian J. of Pharmaceutical Research, 3, 147-153. 6. ArunKaura, Vikas Gupta, Gsroy, Monika Kaura, 2013, International Current Pharmaceutical Journal, 2(5), 97-100. 7. Sandeep Rajurkar, (2011), SIMULTANEOUS DETERMINATION OF CHLORPHENIRAMINE MALEATE, PARACETAMOL AND PSEUDOEPHEDRINE HYDROCHLORIDE IN PHARMACEUTICAL PREPARATIONS BY HPLC. International J. of Life Science and Pharma Research, 1(1), 94-100. 8. Yamato, S.; Sakai, M.; Shimada, K. and YakugakuZasshi, (1996), Quantitative analysis of chlorpheniramine maleate in cough and cold drugs by ion-pair high-performance liquid chromatography for the simultaneous determination of chlorpheniramine and maleate. 116(4), 329-334. 9. Pinak, M.; Sanchaniya, Falgun, A. Mehta and Nirav, B. and Uchadadiya, (2013), Development and Validation of an RP-HPLC Method for Estimation of Chlorpheniramine Maleate, Ibuprofen, and Phenylephrine Hydrochloride in Combined Pharmaceutical Dosage Form. Chromatography Research International , Article ID 424865, 6. 10. Mayano, MA; Rosaco, MA; Pizzorno, MT and Segall, AL, (2005),Validation of an HPLC Method for the Determination of Imatinib Mesylate in Pharmaceutical Dosage. JAOAC Int., 88(6), 1677- 1683. 11. ManfeiXu, Luwei Zhou, Qiao Zhang, Zhisheng Wu, Xinyuan Shi and YanjiangQiae, (2016), J. of innovative Optical Health Sciences, 9(4), 650002 ( 9). 12. Chen ,W.;Liu, F.; Ahang, X.; Lika and Tong, S., Talanta, (2001), 55(1), 29-34. 13. Jun Haginaka and Chino Kagawa, (2002), Uniformly sized molecularly imprinted polymer for d-chlorpheniramine: Evaluation of retention and molecular recognition properties in an aqueous mobile phase. J. of Chromatography A, 948(1-2), 77-84. 14. Walsh, R.; Osmani, Q.; hughes, H.; Duggan ,P. and McLoughlin, (2011), Synthesis of imprinted beads by aqueous suspension polymerisation for chiral recognition of antihistamines, 879930), 3523- 3530. 15. JesikaRane, PriyankaAdhikar and Bakal R. L., (2015),Asian J. of Pharmaceutical technology and Innovation, 3(11), 75-91. 16. Al-Mustafa, J. I.; Abu-Dalu, M. A. and Nassory, N. S., (2014), Int. J. Electrochem. Sci.,m 9, 292. Chemistry |51 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 17. Abu-Dalo, M. A.; Salam, A. A. and Nassory, N. S., (2015), Ion Imprinted Polymer Based Electrochemical Sensor for Environmental Monitoring of Copper(II). Int. J. of Eelectrochem. Sci., 10, 6780. 18. Abu-Dalo, M. A., Nassory, N. S., Abdulla, N. I. and Al-Mheidat, I. R., (2015), Azithromycin-molecularly imprinted polymer based on PVC membrane for Azithromycin determination in drugs using coated graphite electrode J. of Electroanalytical Chemistry, 751, 75. 19. Al-Bayti, Y. K. and Aljabari, F. I., (2016), Synthesis of Ibuprofen – Molecularly Imprinted polymers and used as Sensors to determine the drug in pharmaceutical preparations. Asian J. of Chemistry, 28(6), 1376. 20. Najwa, I. Abdulla and Hamsa, M. Yaseen, (2015), Potentiometric Transducers for the Selective Recognition of Risperidone Based on Molecularly Imprinted Polymer. Iraqi J. Pharma. Sci., 24(2), 30-40. 21. Craggs, A.; Moody, G. J. and Thomas, J. D. R., (1974), PVC matrix membrane ion- selective electrodes. Construction and laboratory experiments. Chem. Edu., 51(8), 541. 22. Bailey, P. L. (ed.), (1976), “Analysis with ion selective electrodes” Published by Heyden& Son LTD.. 23. Umezawa, Y.; Katoka, U. and Hitoshis, S., (1995), Nitrogenous Synergists Induced Potentiometric Response to Metal Ions with Polymeric Liquid Membranes Containing Thenoyltrifluoroacetone as an Ionophore 2006. Pure and Appl. Chem., 67(3), 507-518. 24. Guilbault, G.; Durst, R.; Frant, M. and Thomas, J. D. R., (1976), IUPAC Technical Reports and Recommendations. Pure and Appl. Chem., 48, 127. 25. British Pharmacopoeia (BP), (2000),Vol. 1. Chemistry |52 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Table (1): The most identified peaks of FTIR spectra for CPM and CPM-MIP using (HEMA) as a functional monomer No. Functional Group CPM CPM- MIP(HEMA)before template removal CPM - MIP(HEMA)after template removal 1. OH str.( cm -1 ) 3444 0943 0277 2. N-H str. ( cm -1 ) ---- 0907 ---- 3. Sp3-CH str. ( cm -1 ( 7422 7429 7432 4. C=O str.ester ( cm -1 ) 0230 0279,0202 0273,0202 5. C=C str. ( cm -1 ) 0223 0232 ------ 6. C-O str. Asymm (cm -1 ). 0709 0720 0720 7. C-O str. symm. ( cm -1 ) 0320 0022 0023 8. Out-of plane-para- sub( cm -1 ) 329 864 --- 9. C-Cl str. ( cm -1 ) 220 220 --- Table (2): Electrode parameters of the CPM-MIP and CMP-NIP based on CPM sensor Membrane composition Electrode parameters Slope mV/dec ade Linearity range / M Correlation coefficient Detection limit / M Life time / days Dielectric constant Viscosity cSt CPM-MIP + ToCP (I) 21.00 1x10 -1 –1x10 -5 0.9949 7.0 x 10 -6 ~ 30 6.90 58.0 CPM-MIP + TEHP (II) 21.51 1x10 -1 – 1x10 -5 0.9859 1.0 x 10 -5 ~ 22 4.80 12.0 CPM-MIP + TBP (III) 19.08 1x10 -1 – 2x10 -5 0.9993 4.0 x 10 -6 ~ 10 7.95 3.3 CPM-NIP + ToCP (IV) 12.06 1x10 -1 – 4x10 -3 0.9671 7x10 -3 ~ 2 6.90 58.0 CPM-NIP + TEHP (V) 9.01 1x10 -2 – 1x10 -4 0.8861 3x10 -3 3 4.80 12.0 CPM-NIP + TBP (VI) 11.14 1x10 -2 – 1x10 -5 0.9668 4x10 -4 3 7.95 3.3 Chemistry |53 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Table (3): Results of pH range for the electrodes at three different concentrations of MP Table (4): Selectivity coefficients of some interfering species measured by separate using separate solution method with electrode based on ToCP plasticizer Table (5): Selectivity coefficients of some interfering species measured by separate using separate solution method with electrode based on TEHP plasticizer Number Membrane Composition pH range 1×10 -2 M 1×10 -3 M 1×10 -4 M I CPM- 2HEMA+ToCP 4-8 5.5-8.5 3.5-8 II CPM -2HEMA + TEHP 4-7.5 5-7 3-7.5 III CPM -2HEMA + TBPH 5-8 3.5-6 3-7.5 Selectivity coefficients of interfering species Phenyl alanine Arginine Glycine Alanine Al +3 Mg +2 Na +1 Conc.of CPM M 0.615X10 -2 0.885X10 -2 0.143X10 -2 0.695X10 -3 0.735X10 -3 0.19400 0.11200 10 -1 0.335X10 -2 0.112X10 -2 0.483X10 -2 0.695X10 -2 0.181X10 -3 0.04200 0.12700 10 -2 0.379X10 -2 0.297X10 -2 0.428X10 -2 0.02000 0.027X10 -3 0.280X10 -2 0.16200 10 -3 0.02300 0.10000 0.18300 0.01100 0.110X10 -3 0.233X10 -2 0.42800 10 -4 0.02000 0.06100 0.08800 0.01400 0.021X10 -3 0.280X10 -3 0.54500 10 -5 0.02600 0.20600 0.06100 0.03300 0.971X10 -5 0.162X10 -3 0.88500 10 -6 Selectivity coefficients of interfering species Phenyl alanine Arginine Glycine Alanine Al +3 Mg +2 Na +1 Conc.of CPM M 0.257X10 -3 0.0300 0.820X10 -4 0.0180 0.317X10 -2 0.693X10 -3 0.0370 10 -1 0.801X10 -3 0.0360 0.179X10 -3 0.0160 0.124X10 -2 0.505X10 -3 0.0260 10 -2 0.171X10 -2 0.0420 0.459X10 -3 0.0490 0.600X10 -3 0.460X10 -3 0.0420 10 -3 0.667X10 -2 0.3690 0.164X10 -2 0.8070 0.108X10 -2 0.263X10 -2 0.4570 10 -4 0.991X10 -2 0.2330 0.336X10 -2 0.4150 0.255X10 -3 0.465X10 -3 0.6940 10 -5 0.468X10 -2 0.0580 0.260X10 -2 0.05730 0.670X10 -4 0.561X10 -4 0.3390 10 -6 Chemistry |54 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Table (6): Selectivity coefficients of some interfering species measured by separate using separate solution method with electrode based on TBP plasticizer Table (7): Results of selectivity coefficients measured by mixed solution method of interfering species using membrane I,II and III Table (8): CMP determination in commercial samples by direct and standard addition methods using electrode I Selectivity coefficients of interfering species Phenyl alanine Arginine Glycine Alanine Al +3 Mg +2 Na +1 Conc.of CPM M 0.407X10 -3 0.123X10 -2 0.701X10 -3 0268X10 -2 0.368X10 -3 0.111X10 -2 0.636X10 -2 10 -1 0.128X10 -2 0.467X10 -3 0.724X10 -2 0.0110 0.261X10 -3 0.109X10 -2 0.0160 10 -2 0.636X10 -2 0.0400 0.0640 0.0610 0.375X10 -3 0.265X10 -2 0.0860 10 -3 0.0360 0.1440 0.0570 0.2290 0.339X10 -3 0.191X10 -2 0.2750 10 -4 0.1250 0.2640 0.1960 0.3010 0.145X10 -3 0.138X10 -2 0.3470 10 -5 0.2450 0.1840 0.2180 0.2710 0.582X10 -4 0.762X10 -3 0.3840 10 -6 Electrode No. Conc.of CPM M Na +1 Mg +2 Al +3 Alanine Glycine Arginine Phenyl alanine I 10 -2 0.100 0.011 0.117X10 -2 0.060 0.180 0.080 0.12 10 -3 0.800 0.022 0.189X10 -2 0.300 0.600 0.400 0.31 II 10 -2 0.070 0.311x10 -2 0.175x10 -2 0.040 0.058 0.120 0.038 10 -3 0.340 0.807x10 -2 0.189x10 -2 0.260 0.300 0.400 0.200 III 10 -2 0.180 0.070 0.588X10 -2 2 0.2 0.2 0.2 10 -3 0.020 0.089 0.379X10 -2 10 1.6 1 0.6 %RSD %RE %Rec. Concentration Found/M Prepared Concentration /M Potentiometric methods Pharmaceutical drug 1.5000 1.6000 101.6000 1.016x10 -3 1.0x10 -3 Direct method Tylohol 1.8700 1.3000 101.3000 1.013x10 -3 SAM 0.8600 1.9000 101.9000 1.019x10 -4 1.0x10 -4 Direct method 1.0520 1.4000 101.4000 1.014x10 -4 SAM 1.7800 2.1000 102.1000 1.021x10 -3 1.0x10 -3 Direct method Panadol 0.8070 1.8000 101.8000 1.018x10 -3 SAM 0.6300 2 102 1.02x10 -4 1.0x10 -4 Direct method 1.4000 1.5000 105 1.015x10 -4 SAM Chemistry |55 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Table(9): CMP determination in commercial samples by direct and standard addition methods using electrode II Table (10): CMP determination in commercial samples by direct and standard addition methods using electrode III Figure (1): Structure of chlorpheniramine maleate %RSD %RE %Rec. Concentration Found/M Concentration Prepared/M Potentiometric methods Pharmaceutical drug 1.3000 2 102.1000 1.021x10 -3 1.0x10 -3 Direct method Tylohol 1.4000 1.8000 101.8000 1.018x10 -3 SAM 1.0600 1.3000 101.3000 1.013x10 -4 1.0x10 -4 Direct method 1.7000 1.1000 101.1000 1.011x10 -4 SAM 1.0100 1.7000 101.7000 1.017x10 -3 1.0x10 -3 Direct method Panadol 0.8700 1.5000 101.5000 1.015x10 -3 SAM 1.5000 1.5000 101.5000 1.015x10 -4 1.0x10 -4 Direct method 1.2100 1.3000 101.3000 1.013x10 -4 SAM %RSD %RE %Rec. Concentration Found/M Concentration Prepared/M Potentiometric methods Pharmaceutical drug 1.2000 3 103 1.03x10 -3 1.0x10 -3 Direct method Tylohol 0.9700 2.500 102.5000 1.025x10 -3 SAM 1.3000 2.6000 102.6000 1.026x10 -4 1.0x10 -4 Direct method 1.1000 2 102 1.02x10 -4 SAM 1.3700 2.3000 102.3000 1.023x10 -3 1.0x10 -3 Direct method Panadol 1.5000 1.6000 101.6000 1.016x10 -3 SAM 1.4000 2.1000 102.1000 1.021x10 -4 1.0x10 -4 Direct method 1.2000 1.9000 101.9000 1.019x10 -4 SAM Chemistry |56 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 180 160 140 120 100 80 60 40 -7 -6 -5 -4 -3 -2 -1 0 Log[CPM] Figure (2): Schematic representation of the non-covalent and covalent molecular procedures prints a b Figure (3): SEM photographs of the surface of MIP, a) before washing b) after washing. Figure (4):Calibration curves of CMP-MIP electrodes using; ◊-TBP, Δ-TEHP and □- ToCP as Plasticizer Chemistry |57 160110.30526/30.3.https://doi.org/ 7302(عام 0العدد ) 03مجلة إبن الهيثم للعلوم الصرفة والتطبيقية المجلد Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 30 (3) 2017 Figure (5):Plot of electrode response with pH of electrode based on ToCP plasticizer at three different of CMP concentrations; Δ-10 -4 M, □-10 -3 M and ◊-10 -2 M Figure (6): Plot of log K of interfering species at concentration 10 -3 M of CMP; 1-Na + , 2- Mg +2 , 3-Al +3 , 4-glycine, 5-alanine, 6-arginine and 7-phenyl alanine. Coc of interference Na + Mg +2 Al +3 Glycine Alanine Arginine Phenylalanine E le ct ro d e re sp o n se /m V p H 140 130 120 110 100 90 80 70 0 5 10 10