Hidroksizinin Tablet Formülasyonunda Analizi için Yeni Bir RP-HPLC Tekniği

Alerji ilaçları, alerjik reaksiyonları hafifletmek ve semptomları kontrol altına almak için kullanılan farmasötik ürünlerdir. Günümüzde alerji ilaçlarının önemi, artan alerjik hastalık prevalansı ve semptomların etkili bir şekilde yönetilmesinin gerekliliği nedeniyle giderek artmaktadır. Bu araştırmada alerjik bir ilaç olan hidroksizinin tayin edilmesinde yeni bir metot önerilmiştir. Bu araştırmanın amacı, tablet formundaki piperazin türevi ilaç etken maddesi hidroksizini analiz etmek için bir RP-HPLC metodu geliştirmek ve doğrulamaktır. Optimum sıvı kromatografik ayırma koşullarını belirlemek için mobil faz pH'ı ile alıkonma süresi arasındaki korelasyona dayanan sistematik bir yaklaşım kullanılmıştır. Hidroksizinin tayini, Xbridge C18 kolonunda (3 um, 150 x 4,6 mm, I.D.), pH 6'ya ayarlanmış %45 (v/v) asetonitril içeren asetonitril-su ikili karışımında sağlanmıştır. Çalışma 0,8 mL/dakika akış hızında, 37 °C kolon sıcaklığı ve 230 nm dalga boyunda gerçekleştirilmiştir.

Anahtar Kelimeler:

Hidroksizin, metot validasyonu, piperazin, RP-HPLC

A Novel RP-HPLC Technique for the Analysis of Hydroxyzine in Tablet Formulation

Allergy medications are pharmaceutical products used to alleviate allergic reactions and control symptoms. The importance of allergy medications in today's world is increasingly recognized due to the rising prevalence of allergic diseases and the necessity for effective symptom management. In this study, a new method is proposed for the determination of hydroxyzine, an antiallergic drug.The aim of this research was to develop and validate an RP-HPLC method to analyze the piperazine-derived drug active ingredient hydroxyzine in tablet form. A systematic approach based on the correlation between mobile phase pH and retention time was used to determine the optimum liquid chromatographic separation conditions. The determination of hydroxyzine was achieved on an Xbridge C18 column (3 μm, 150 x 4.6 mm, I.D.) in an acetonitrile-water binary mixture containing 45% (v/v) acetonitrile adjusted to pH 6. The run was performed at a flow rate of 0.8 mL/min, column temperature of 37 °C and wavelength of 230 nm.

Keywords:

hydroxyzine, method validation, piperazines, RP-HPLC,

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[1] Pettersson, M. E., Koppelman, G. H., Flokstra‐de Blok, B. M., Kollen, B. J., & Dubois, A. E. 2018. Prediction of the severity of allergic reactions to foods. Allergy, 73(7), 1532-1540.
[2] Maintz, L., & Novak, N. 2007. Histamine and histamine intolerance. The American journal of clinical nutrition, 85(5), 1185-1196
[3] Thurmond, R. L., Desai, P. J., Dunford, P. J., Fung-Leung, W. P., Hofstra, C. L., Jiang, W., ... & Karlsson, L. 2004. A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. Journal of Pharmacology and Experimental Therapeutics, 309(1), 404-413.
[4] Laszlo, V., Rothe, G., Hegyesi, H., Szeberenyi, J. B., Orsoó, E., Schmitz, G., & Falus, A. 2001. Increased histidine decarboxylase expression during in vitro monocyte maturation; a possible role of endogenously synthesised histamine in monocyte/macrophage differentiation. Inflammation Research, 50, 428-434.
[5] Simons, F. E. R. 2004. Advances in H1-antihistamines. New England Journal of Medicine, 351(21), 2203-2217.
[6] Schaefer, U., Schmitz, V., Schneider, A., & Neugebauer, E. 1999. Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial cells. Shock (Augusta, Ga.), 12(4), 309-315.
[7] Dimitriadou, V., Pang, X., & Theoharides, T. C. 2000. Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated brain mast cell activation. International journal of immunopharmacology, 22(9), 673-684.
[8] Kintz, P., Godelar, B., & Mangin, P. 1990. Gas chromatographic identification and quantification of hydroxyzine: application in a fatal self-poisoning. Forensic science international, 48(2), 139-143.
[9] Ackermann, H., Kretzschmann, F., Krüger, S., & Lexow, B. 1977. Thin-layer chromatographic technic for the semiquantitative determination of hydroxyzine residues in animal material. Die Nahrung, 21(7), 603-610.
[10] Martinez-Algaba, C., Bermudez-Saldana, J. M., Villanueva-Camanas, R. M., Sagrado, S., & Medina-Hernández, M. 2006. Analysis of pharmaceutical preparations containing antihistamine drugs by micellar liquid chromatography. Journal of pharmaceutical and biomedical analysis, 40(2), 312-321.
[11] Capella-Peiro, M. E., Bossi, A., & Esteve-Romero, J. 2006. Optimization by factorial design of a capillary zone electrophoresis method for the simultaneous separation of antihistamines. Analytical biochemistry, 352(1), 41-49.
[12] Beltagi, A. M., Abdallah, O., & Ghoneim, M. M. 2008. Development of a voltammetric procedure for assay of the antihistamine drug hydroxyzine at a glassy carbon electrode: Quantification and pharmacokinetic studies. Talanta, 74(4), 851-859.
[13] Zhou, N., Liang, Y. Z., Chen, B. M., Wang, P., Chen, X., & Liu, F. P. 2007. Development and validation of LC–MS method for the determination of hydroxyzine hydrochloride in human plasma and subsequent application in a bioequivalence study. Chromatographia, 66, 481-486.
[14] Bouklouze, A., Elbouzekraoui, M., Cherrah, Y., Hassar, M., & Kauffmann, J. M. 2002. Potentiometric sensor for hydroxyzine determination. Electroanalysis: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis, 14(19‐20), 1369-1374.
[15] Ciaccio, L. L., Missan, S. R., McMullen, W. H., & Grenfell, T. C. 1957. Nonaqueous titration of 1, 4-Disubstituted piperazines. Analytical Chemistry, 29(11), 1670-1673.
[16] Pasich J, Stasiewska K.1962. Simple gravimetric determination of hydroxyzine, diprophylline, chlorpromazine and ethionamide in suppositories. Acta Poloniae Pharmaceutica, 1962;(19):181-182.
[17] Basavaiah, K., & Charan, V. S. 2002. Titrimetric and spectrophotometric assay of some antihistamines through the determination of the chloride of their hydrochlorides. Il Farmaco, 57(1), 9-17.
[18] 18. Rajendraprasad, N., & Basavaiah, K. 2013. Titrimetric assay of hydroxyzine dihydrochloride in pharmaceuticals and formulations in non-aqueous medium. International Journal of PharmTech Research, 5(1), 105-111.
[19] Rajendraprasad, N., Basavaiah, K., Vinay, K. B., & Revanasiddappa, H. D. 2010. Sensitive and selective extractive spectrophotometric method for the determination of hydroxyzine dihydrochloride in pharmaceuticals. Journal of the Mexican Chemical Society, 54(4), 233-239.
[20] Péhourcq, F. 2004. A simple high-performance liquid chromatographic method for detection of hydroxyzine in human plasma after overdose. Journal of pharmacological and toxicological methods, 50(1), 41-44.
[21] Sher, N., Siddiqui, F. A., Fatima, N., Perveen, S., & Shafi, N. 2015. New method development for hydroxyzine determination: application in stability studies, pharmaceutical formulations, and humane serum. Journal of Liquid Chromatography & Related Technologies, 38(8), 911-918.
[22] Snyder, L. R., Kirkland, J. J., & Dolan, J. W. 2011. Introduction to modern liquid chromatography. John Wiley & Sons.
[23] ICH, Validation of Analytical Procedures: Text and Methodology Q2 (R1) Harmonized Tripartite Guideline 2005.
[24] Daldal, Y. D., & Demiralay, E. Ç. 2022. Development of liquid chromatographic and UV-visible spectrophotometric methods for determination of pKa values of folic acid antimetabolites. Journal of Pharmaceutical and Biomedical Analysis, 212, 114647.
[25] Yılmaz, H., Üstün, Z., & Çubuk Demiralay, E. 2016. RPLC determination of acid dissociation constants and quantitative estimation for sulfasalazine. Journal of the Iranian Chemical Society, 13, 103-110.
[26] Demiralay, E. Ç., Ürer, F., Üstün, Z., & Daldal, Y. D. 2023. RPLC Method Development And Validation For The Simultaneous Determination Of Selective Serotonin Reuptake Inhibitors In Tablet Formulations. Journal of Faculty of Pharmacy of Ankara University, 47(2), 7-7.
[27] Vonaparti, A., Kazanis, M., & Panderi, I. 2006. Development and validation of a liquid chromatographic/electrospray ionization mass spectrometric method for the determination of benazepril, benazeprilat and hydrochlorothiazide in human plasma. Journal of mass spectrometry, 41(5), 593-605.
[28] Paszun, S. K., Stanisz, B., & Pawłowski, W. 2012. Rapid and simple stability indicating HPLC method for the determination of cilazapril in pure substance and pharmaceutical formulation in comparison with classic and derivative spectrophotometric methods. Acta Poloniae Pharmaceutica, 69(2), 193-201.
[29] Kuzucanlı, E., Demiralay, E. Ç., Daldal, Y. D., Üstün, Z., Konçe, İ., & Alsancak, A. G. (2022). Development and validation of RPLC method for the simultaneous analysis of ACE inhibitors in tablet formulations. Turkish Journal of Analytical Chemistry, 4(2), 103-110.