Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

Author(s): Bahareh Sadat Yousefsani, Seyed Ahmad Mohajeri, Mohammad Moshiri, Hossein Hosseinzadeh*.

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.

Objective: An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.

Methods: A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.

Results: The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.

Conclusion: The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

Keywords: Clozapine, molecularly imprinted polymer, solid-phase extraction, HPLC-UV, intravenous lipid emulsion.

Cadeddu, G.; Deidda, A.; Stochino, M.E.; Velluti, N.; Burrai, C.; Del Zompo, M. Clozapine toxicity due to a multiple drug interaction: a case report. J. Med. Case Rep, 2015, 9, 77.
Abanmy, N.O.; Al-Jaloud, A.; Al-Jabr, A.; Al-Ruwaisan, R.; Al-Saeed, W.; Fatani, S. Clozapine-induced blood dyscrasias in Saudi Arab patients. Int. J. Clin. Pharm., 2014, 36, 815-820.
Abou, F.K.; van Vliet, A.; Knegtering, H.; Bruggeman, R. The value of desmethylclozapine and serum CRP in clozapine toxicity: a case report. Case Rep. Psychiatry, 2012, 2012, 592784.
Leung, J.G.; Nelson, S.; Takala, C.R.; Goren, J.L. Infection and inflammation leading to clozapine toxicity and intensive care: a case series. Ann. Pharmacother., 2014, 48, 801-805.
Kaur, H.; Bassi, P.; Monif, T.; Khuroo, A.; Kaur, G. Development and validation of high performance liquid chromatographic method for analysis of clozapine. Pak. J. Pharm. Sci., 2013, 26, 465-472.
Hadizadeh, F.; Moghadam, M.H.; Mohajeri, S.A. Application of molecularly imprinted hydrogel for the preparation of lactose-free milk. J. Sci. Food Agric., 2013, 93, 304-309.
Sahebnasagh, A.; Karimi, G.; Mohajeri, S.A. Preparation and evaluation of histamine imprinted polymer as a selective sorbent in molecularly imprinted solid-phase extraction coupled with high performance liquid chromatography analysis in canned fish. Food Anal. Methods, 2014, 7, 1-8.
Rahmani, A.; Mohammadpour, A.H.; Sahebnasagh, A.; Mohajeri, S.A. Haloperidol imprinted polymer: preparation, evaluation, and application for drug assay in brain tissue. Anal. Bioanal. Chem., 2014, 406, 7729-7739.
Mohajeri, S.A.; Ebrahimi, S.A. Preparation and characterization of a lamotrigine imprinted polymer and its application for drug assay in human serum. J. Sep. Sci., 2008, 31, 3595-3602.
Malaekeh-Nikouei, B.; Vahabzadeh, S.A.; Mohajeri, S.A. Preparation of a molecularly imprinted soft contact lens as a new ocular drug delivery system for dorzolamide. Curr. Drug Del., 2013, 10, 279-285.
Javanbakht, M.; Attaran, A.M.; Namjumanesh, M.H.; Esfandyari-Manesh, M.; Akbari-Adergani, B. Solid-phase extraction of tramadol from plasma and urine samples using a novel water-compatible molecularly imprinted polymer. J. Chromatog. B Anal. Tech. Biomed. Life Sci., 2010, 878, 1700-1706.
Haupt, K. Molecularly imprinted polymers in analytical chemistry. Analyst , 2001, 126, 747-756.
Claude, B.; Viron-Lamy, C.; Haupt, K.; Morin, P. Synthesis of a Molecularly Imprinted Polymer for the Solid-phase Extraction of Betulin and Betulinic Acid from Plane Bark. Phytochem. Anal., 2010, 21, 180-185.
Mohajeri, S.A.; Malaekeh-Nikouei, B.; Sadegh, H. Development of a pH-responsive imprinted polymer for diclofenac and study of its binding properties in organic and aqueous media. Drug Dev. Ind. Pharm., 2012, 38, 616-622.
Seyed, A.M.; Hosseinzadeh, H.; Keyhanfar, F.; Aghamohammadian, J. Extraction of crocin from saffron (Crocus sativus) using molecularly imprinted polymer solid-phase extraction. Clin. Biochem., 2011, 44, S136-S136.
Hadizadeh, F.; Zakerian, A.; Mohajeri, S.A. Non-covalently lactose imprinted polymers and recognition of saccharides in aqueous solutions. J. Iranian Chem. Soc., 2013, 10, 207-212.
Fan, J.; Wei, Y.F.; Wang, J.J.; Wu, C.L.; Shi, H.L. Study of molecularly imprinted solid-phase extraction of diphenylguanidine and its structural analogs. Analytica. Chimica Acta, 2009, 639, 42-50.
Sun, H.W.; Qiao, F.X.; Liu, G.Y. Characteristic of theophylline imprinted monolithic column and its application for determination of xanthine derivatives caffeine and theophylline in green tea. J. Chromatog. A, 2006, 1134, 194-200.
Alizadeh, T.; Zare, M.; Ganjali, M.R.; Norouzi, P.; Tavana, B. A new molecularly imprinted polymer (MIP)-based electrochemical sensor for monitoring 2,4,6-trinitrotoluene (TNT) in natural waters and soil samples. Biosensors Bioelectronics., 2010, 25, 1166-1172.
Malaekeh-Nikouei, B.; Ghaeni, F.A.; Motamedshariaty, V.S.; Mohajeri, S.A. Controlled release of prednisolone acetate from molecularly imprinted hydrogel contact lenses. J. Appl. Polymer. Sci., 2012, 126, 387-394.
Mohajeri, S.A.; Malaekeh-Nikouei, B.; Sadegh, H. Development of a pH-responsive imprinted polymer for diclofenac and study of its binding properties in organic and aqueous media. Drug Develop. Industrial Pharm, 2012, 38, 616-622.
Mohajeri, S.A.; Karimi, G.; Khansari, M.R. Clozapine imprinted polymers: synthesis, characterization and application for drug assay in human serum. Analytica. Chimica. Acta, 2010, 683, 143-148.
Cave, G.; Harvey, M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad. Emergency . Med., 2009, 16, 815-824.
Szadkowski, M.; Caravati, E.M.; Gamboa, D.; Dudley, N. Treatment of flecainide toxicity in a 12-month-old child using intravenous lipid emulsion. Clinical. Toxicol. , 2015, 53, 724-724.
Schult, R.; Gorodetsky, R.M.; Wiegand, T.J. Intravenous lipid emulsion for amlodipine/benazepril toxicity: A case report. Clinical. Toxicol., 2015, 53, 251-252.
Carreiro, S.; Hack, J.B.; Blum, J. Lipid emulsion for cocaine toxicity: more questions for investigation reply. Annals. Emergency. Med., 2015, 65, 127-128.
Mohajeri, S.A.; Hosseinzadeh, H.; Keyhanfar, F.; Aghamohammadian, J. Extraction of crocin from saffron (Crocus sativus) using molecularly imprinted polymer solid-phase extraction. J. Separation . Sci., 2010, 33, 2302-2309.
Moshiri, M.; Mohammadpour, A.H.; Vahabzadeh, M.; Etemad, L.; Memar, B.; Hosseinzadeh, H. Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit. Biomed Res. Int., 2014, 2014, 949262.
Moshiri, M.; Vahabzadeh, M.; Mohammadpour, A.H.; Hosseinzadeh, H. Evaluation of intravenous lipid emulsion on haloperidol-induced hypotension in rabbits. Toxicol. Ind. Health, 2016, 32(5), 945-952.
Vahabzadeh, M.; Hoseinzadeh, H. Promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning. Toxicol. Lett., 2013, 221, S94-S94.
Harvey, M.; Cave, G. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Annals. Emergency. Med., 2007, 49, 178-185.
Ulrich, S.; Kruggel, S.; Weigmann, H.; Hiemke, C. Fishing for a drug: solid-phase microextraction for the assay of clozapine in human plasma. J. Chromatogr. B Biomed. Sci. Appl., 1999, 731, 231-240.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [251 - 257]
Pages: 7
DOI: 10.2174/1573412914666180111160741
Price: $65

Article Metrics

PDF: 20
PRC: 1