Analytical Method Validation and Simultaneous Determination of Ketotifen Fumarate and Cyproheptadine Hydrochloride in Divided Powder by RP-HPLC Method
Keywords:
cyproheptadine hydrochloride, ketotifen fumarate, HPLC, validation
Abstract
Ketotifen fumarate and cyproheptadine HCl are the most popular prescription for children at “X” hospital in Yogyakarta. The interest for studying this divided powder was related to the stability test towards human health. Hence, it was important to developed a validated analytical method to quantify content of active drug from sample. In this study, a reversed phase HPLC (RP-HPLC) method was validated and applied for determining content of ketotifen fumarate and cyproheptadine hydrochloride in divided powder. The developed RP-HPLC method was met the requirement of selectivity and sensitivity. Calibration curve formulas of ketotifen fumarate and cyproheptadine hydrochloride were y = 27714x-79111 (r=0.9945) and y = 26324x+72581 (r=0.9935) in the range of 10.9-54.5 and 10.6-53.0 µg/mL, respectively. Accuracy and intermediate precision were assessed on both standard solution and samples spiked with standard solution of ketotifen fumarate and cyproheptadine hydrochloride. It was found that both standard solution and the spiked samples solution were met the requirement of recovery of 80-110% and RSD of less than 7.3% for intraday and interday analysis. Content of ketotifen fumarate and cyproheptadine hydrochloride in sample (n=7) were 16.574±0.098 and 30.640±0.035 µg/mL, respectively. It can be concluded that the RP-HPLC method was successfully validated and applied in the determination of ketotifen fumarate and cyproheptadine hydrochloride in divided powder.
References
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El-Kommos, M.E., El-Gizawy, S.M., Atia, N.N., Hosny, N.M., 2015. Analysis for commonly prescribed non-sedating antihistamines. Anal. Chem. Res. 3, 1–12. https://doi.org/10.1016/j.ancr.2014.11.003
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Kuna, P., Jurkiewicz, D., Czarnecka-Operacz, M.M., Pawliczak, R., Woron, J., Moniuszko, M., Emeryk, A., 2016. The role and choice criteria of antihistamines in allergy management - expert opinion. Postep. Dermatologii i Alergol. 33, 397–410. https://doi.org/10.5114/pdia.2016.63942
Mangundap, S.A., Malik, S.A., 2023. Prevalence, Management, and Risk Factor of Asthma Among School-Age Children in Yogyakarta, Indonesia. J. Asthma Allergy 16, 105–106. https://doi.org/10.2147/JAA.S404674
Marcos, L.G., Asher, M.I., Pearce, N., Ellwood, E., Bissell, K., Chiang, C.Y., Sony, A.E., Ellwood, P., 2022. The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study. Eur. Respir. J. 60. https://doi.org/10.1183/13993003.02286-2021
Mennickent, S., de Diego, M., 2019. Analytical Method Validation as the First Step in Drug Quality Control. Qual. Manag. Qual. Control - New Trends Dev. 1–21. https://doi.org/10.5772/intechopen.82826
Miller, J.N., Miller, J.C., Miller, R.D., 2018. Statistics and Chemometrics for Analytical Chemistry, Seventh Ed. ed. Pearson Education Limited, Harlow.
Mohammed, O.J., Hamzah, M.J., Saeed, A.M., 2021. RP – HPLC Method Validation for Simultaneous Estimation of Paracetamol and Caffeine in Formulating Pharmaceutical Form. Res. J. Pharm Tech. 14, 4743–4748. https://doi.org/10.52711/0974-360X.2021.00825
Moreno, D., Sobarzo, C.M., Lustig, L., Pena, M.G.R., Guazzone, V.A., 2020. Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord. Asian J. Androl. 22, 112–117. https://doi.org/10.4103/aja.aja
Peikova, L., Tzankova, D., Smerikarova, M., Balkanski, S., Zlatkov, A., 2022. Development of RP-HPLC Methods for the Analysis of Dexamethasone and Levofloxacin Alone and in Combinations used in the Therapy of Covid-19. Pharmacia 69, 1075–1080. https://doi.org/10.3897/pharmacia.69.e97779
Pozharani, L.B., Burgaz, E.., Baloglu, E., 2022. Development and Validation of an RP-HPLC Method for Simultaneous Determination of Curcumin and Metronidazole in Combined Dosage Form. Instanbul J Pharm 52, 250–257. https://doi.org/10.26650/IstanbulJPharm.2022.1005453
Prasad, P.R., Karunakar, D., Devi, B.R., 2022. Analytical Method Development and Validation of Allopurinol and Related Substances by using RP-HPLC in Bulk Form. Int. J. Health Sci. (Qassim). 6, 10447–10470.
Rajput, S.J., Sathe, M.A., 2019. New bioanalytical HPLC method for the determination of cyproheptadine hydrochloride in human plasma and its application to rat pharmacokinetic study. Indian J. Pharm. Educ. Res. 53, S338–S346. https://doi.org/10.5530/ijper.53.3s.104
Sahai, M., Devanna, N., 2021. Validated Stability Indicating HPLC Approach for Quantifying Tricholine Citrate and Cyproheptadine Simultaneously in Syrup Forms. Int. J. Appl. Pharm. 13, 207–213. https://doi.org/10.22159/ijap.2021v13i3.40871
Sethiya, A., Rathore, R.P.., 2022. RP-HPLC Method Development and Validation for the Estimation of Artemisinin in Bulk Drug. Int. J. Health Sci. (Qassim). 6, 14037–14045.
Snyder, L., Kirkland, J.J., Dolan, J.., 2010. Introduction to Modern Liquid Chromatography, Third Edition, Journal of the American Society for Mass Spectrometry. https://doi.org/10.1007/s13361-010-0021-8
Soriano, J.B., Abajobir, A.A., Abate, K.H., Abera, S.F., Agrawal, A., Ahmed, M.B., Aichour, A.N., Aichour, I., Eddine Aichour, M.T., Alam, K., Alam, N., Alkaabi, J.M., Al-Maskari, F., Alvis-Guzman, N., Amberbir, A., Amoako, Y.A., Ansha, M.G., Antó, J.M., Asayesh, H., Atey, T.M., Avokpaho, E.F.G.A., Barac, A., Basu, S., Bedi, N., Bensenor, I.M., Berhane, A., Beyene, A.S., Bhutta, Z.A., Biryukov, S., Boneya, D.J., Brauer, M., Carpenter, D.O., Casey, D., Christopher, D.J., Dandona, L., Dandona, R., Dharmaratne, S.D., Do, H.P., Fischer, F., Gebrehiwot, T.T., Geleto, A., Ghoshal, A.G., Gillum, R.F., Mohamed Ginawi, I.A., Gupta, V., Hay, S.I., Hedayati, M.T., Horita, N., Hosgood, H.D., Jakovljevic, M.M.B., James, S.L., Jonas, J.B., Kasaeian, A., Khader, Y.S., Khalil, I.A., Khan, E.A., Khang, Y.H., Khubchandani, J., Knibbs, L.D., Kosen, S., Koul, P.A., Kumar, G.A., Leshargie, C.T., Liang, X., Magdy Abd El Razek, H., Majeed, A., Malta, D.C., Manhertz, T., Marquez, N., Mehari, A., Mensah, G.A., Miller, T.R., Mohammad, K.A., Mohammed, K.E., Mohammed, S., Mokdad, A.H., Naghavi, M., Nguyen, C.T., Nguyen, G., Nguyen, Q. Le, Nguyen, T.H., Ningrum, D.N.A., Nong, V.M., Obi, J.I., Odeyemi, Y.E., Ogbo, F.A., Oren, E., Mahesh, P.A., Park, E.K., Patton, G.C., Paulson, K., Qorbani, M., Quansah, R., Rafay, A., Rahman, M.H.U., Rai, R.K., Rawaf, S., Reinig, N., Safiri, S., Sarmiento-Suarez, R., Sartorius, B., Savic, M., Sawhney, M., Shigematsu, M., Smith, M., Tadese, F., Thurston, G.D., Topor-Madry, R., Tran, B.X., Ukwaja, K.N., van Boven, J.F.M., Vlassov, V.V., Vollset, S.E., Wan, X., Werdecker, A., Hanson, S.W., Yano, Y., Yimam, H.H., Yonemoto, N., Yu, C., Zaidi, Z., Sayed Zaki, M. El, Lopez, A.D., Murray, C.J.L., Vos, T., 2017. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med. 5, 691–706. https://doi.org/10.1016/S2213-2600(17)30293-X
Vardanyan, R., 2017. Piperidin-4-Ylidene Substituted Tricyclic Compounds, Piperidine-Based Drug Discovery. https://doi.org/10.1016/b978-0-12-805157-3.00006-5
Yilmaz, B., Bayrak, B., Kadioglu, Y., 2022. Development and Validation of HPLC Method for the Determination of Flurbiprofen in Pharmaceutical Preparations. Int. J. PharmATA 2, 72–81.
Yuliani, S.H., Putri, D.C.A., Widayati, A., Abiyoga, B., 2020. Compounding practice in a developing country: A case study of divided powder in Indonesia. Res. J. Pharm. Technol. 13, 6231–6237. https://doi.org/10.5958/0974-360X.2020.01086.0
Aldewachi, H., Omar, T.A., 2022. Development of HPLC Method for Simultaneous Determination of Ibuprofen and Chlorpheniramine Maleate. Sci. Pharm. 90, 1–9.
AOAC International, 2019. Official Methods Of Analysis.
Asher, I., Pearce, N., 2014. Global burden of asthma among children. Int. J. Tuberc. Lung Dis. 18, 1269–1278. https://doi.org/10.5588/ijtld.14.0170
Basharat, R., Kotra, V., Loong, L.., Mathews, A., Kanakal, M.., Devi, C.B.., 2021. Ultra Performance Liquid Chromatography (Mini-Review) RAbIA. Orient. J. Chem. 37, 847–857. https://doi.org/10.13005/ojc/370411
Chakraborty, A., 2019. Role of Cyproheptadine in Various Psychiatric Conditions. Indian J. Priv. Psychiatry 13, 58–61. https://doi.org/10.5005/jp-journals-10067-0034
Chaudhari, N.K., 2014. Rp-Hplc Method Development and Validation of Ketotifen Fumarate and Theophylline in Bulk and Combined Dosage Form. Int. Res. J. Pharm. 5, 407–411. https://doi.org/10.7897/2230-8407.050585
Dzulfianto, A., Riswanto, F.D.O., Rohman, A., 2017. The employment of UV-spectroscopy combined with multivariate calibration for analysis of paracetamol, propyphenazone and caffeine. Indones. J. Pharm. 28, 191–197. https://doi.org/10.14499/indonesianjpharm28iss4pp191
El-Kommos, M.E., El-Gizawy, S.M., Atia, N.N., Hosny, N.M., 2015. Analysis for commonly prescribed non-sedating antihistamines. Anal. Chem. Res. 3, 1–12. https://doi.org/10.1016/j.ancr.2014.11.003
Gebretsadik, H., Kahsay, G., Eticha, T., Gebretsadikan, T., 2023. A Validated New RP-HPLC Method for Simultaneous Determination of Amoxicillin, Ampicillin and Cloxacillin in Pharmaceutical Formulations. Acta Chromatogr. 35, 193–203. https://doi.org/10.1556/1326.2022.01043
Kuna, P., Jurkiewicz, D., Czarnecka-Operacz, M.M., Pawliczak, R., Woron, J., Moniuszko, M., Emeryk, A., 2016. The role and choice criteria of antihistamines in allergy management - expert opinion. Postep. Dermatologii i Alergol. 33, 397–410. https://doi.org/10.5114/pdia.2016.63942
Mangundap, S.A., Malik, S.A., 2023. Prevalence, Management, and Risk Factor of Asthma Among School-Age Children in Yogyakarta, Indonesia. J. Asthma Allergy 16, 105–106. https://doi.org/10.2147/JAA.S404674
Marcos, L.G., Asher, M.I., Pearce, N., Ellwood, E., Bissell, K., Chiang, C.Y., Sony, A.E., Ellwood, P., 2022. The burden of asthma, hay fever and eczema in children in 25 countries: GAN Phase I study. Eur. Respir. J. 60. https://doi.org/10.1183/13993003.02286-2021
Mennickent, S., de Diego, M., 2019. Analytical Method Validation as the First Step in Drug Quality Control. Qual. Manag. Qual. Control - New Trends Dev. 1–21. https://doi.org/10.5772/intechopen.82826
Miller, J.N., Miller, J.C., Miller, R.D., 2018. Statistics and Chemometrics for Analytical Chemistry, Seventh Ed. ed. Pearson Education Limited, Harlow.
Mohammed, O.J., Hamzah, M.J., Saeed, A.M., 2021. RP – HPLC Method Validation for Simultaneous Estimation of Paracetamol and Caffeine in Formulating Pharmaceutical Form. Res. J. Pharm Tech. 14, 4743–4748. https://doi.org/10.52711/0974-360X.2021.00825
Moreno, D., Sobarzo, C.M., Lustig, L., Pena, M.G.R., Guazzone, V.A., 2020. Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord. Asian J. Androl. 22, 112–117. https://doi.org/10.4103/aja.aja
Peikova, L., Tzankova, D., Smerikarova, M., Balkanski, S., Zlatkov, A., 2022. Development of RP-HPLC Methods for the Analysis of Dexamethasone and Levofloxacin Alone and in Combinations used in the Therapy of Covid-19. Pharmacia 69, 1075–1080. https://doi.org/10.3897/pharmacia.69.e97779
Pozharani, L.B., Burgaz, E.., Baloglu, E., 2022. Development and Validation of an RP-HPLC Method for Simultaneous Determination of Curcumin and Metronidazole in Combined Dosage Form. Instanbul J Pharm 52, 250–257. https://doi.org/10.26650/IstanbulJPharm.2022.1005453
Prasad, P.R., Karunakar, D., Devi, B.R., 2022. Analytical Method Development and Validation of Allopurinol and Related Substances by using RP-HPLC in Bulk Form. Int. J. Health Sci. (Qassim). 6, 10447–10470.
Rajput, S.J., Sathe, M.A., 2019. New bioanalytical HPLC method for the determination of cyproheptadine hydrochloride in human plasma and its application to rat pharmacokinetic study. Indian J. Pharm. Educ. Res. 53, S338–S346. https://doi.org/10.5530/ijper.53.3s.104
Sahai, M., Devanna, N., 2021. Validated Stability Indicating HPLC Approach for Quantifying Tricholine Citrate and Cyproheptadine Simultaneously in Syrup Forms. Int. J. Appl. Pharm. 13, 207–213. https://doi.org/10.22159/ijap.2021v13i3.40871
Sethiya, A., Rathore, R.P.., 2022. RP-HPLC Method Development and Validation for the Estimation of Artemisinin in Bulk Drug. Int. J. Health Sci. (Qassim). 6, 14037–14045.
Snyder, L., Kirkland, J.J., Dolan, J.., 2010. Introduction to Modern Liquid Chromatography, Third Edition, Journal of the American Society for Mass Spectrometry. https://doi.org/10.1007/s13361-010-0021-8
Soriano, J.B., Abajobir, A.A., Abate, K.H., Abera, S.F., Agrawal, A., Ahmed, M.B., Aichour, A.N., Aichour, I., Eddine Aichour, M.T., Alam, K., Alam, N., Alkaabi, J.M., Al-Maskari, F., Alvis-Guzman, N., Amberbir, A., Amoako, Y.A., Ansha, M.G., Antó, J.M., Asayesh, H., Atey, T.M., Avokpaho, E.F.G.A., Barac, A., Basu, S., Bedi, N., Bensenor, I.M., Berhane, A., Beyene, A.S., Bhutta, Z.A., Biryukov, S., Boneya, D.J., Brauer, M., Carpenter, D.O., Casey, D., Christopher, D.J., Dandona, L., Dandona, R., Dharmaratne, S.D., Do, H.P., Fischer, F., Gebrehiwot, T.T., Geleto, A., Ghoshal, A.G., Gillum, R.F., Mohamed Ginawi, I.A., Gupta, V., Hay, S.I., Hedayati, M.T., Horita, N., Hosgood, H.D., Jakovljevic, M.M.B., James, S.L., Jonas, J.B., Kasaeian, A., Khader, Y.S., Khalil, I.A., Khan, E.A., Khang, Y.H., Khubchandani, J., Knibbs, L.D., Kosen, S., Koul, P.A., Kumar, G.A., Leshargie, C.T., Liang, X., Magdy Abd El Razek, H., Majeed, A., Malta, D.C., Manhertz, T., Marquez, N., Mehari, A., Mensah, G.A., Miller, T.R., Mohammad, K.A., Mohammed, K.E., Mohammed, S., Mokdad, A.H., Naghavi, M., Nguyen, C.T., Nguyen, G., Nguyen, Q. Le, Nguyen, T.H., Ningrum, D.N.A., Nong, V.M., Obi, J.I., Odeyemi, Y.E., Ogbo, F.A., Oren, E., Mahesh, P.A., Park, E.K., Patton, G.C., Paulson, K., Qorbani, M., Quansah, R., Rafay, A., Rahman, M.H.U., Rai, R.K., Rawaf, S., Reinig, N., Safiri, S., Sarmiento-Suarez, R., Sartorius, B., Savic, M., Sawhney, M., Shigematsu, M., Smith, M., Tadese, F., Thurston, G.D., Topor-Madry, R., Tran, B.X., Ukwaja, K.N., van Boven, J.F.M., Vlassov, V.V., Vollset, S.E., Wan, X., Werdecker, A., Hanson, S.W., Yano, Y., Yimam, H.H., Yonemoto, N., Yu, C., Zaidi, Z., Sayed Zaki, M. El, Lopez, A.D., Murray, C.J.L., Vos, T., 2017. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med. 5, 691–706. https://doi.org/10.1016/S2213-2600(17)30293-X
Vardanyan, R., 2017. Piperidin-4-Ylidene Substituted Tricyclic Compounds, Piperidine-Based Drug Discovery. https://doi.org/10.1016/b978-0-12-805157-3.00006-5
Yilmaz, B., Bayrak, B., Kadioglu, Y., 2022. Development and Validation of HPLC Method for the Determination of Flurbiprofen in Pharmaceutical Preparations. Int. J. PharmATA 2, 72–81.
Yuliani, S.H., Putri, D.C.A., Widayati, A., Abiyoga, B., 2020. Compounding practice in a developing country: A case study of divided powder in Indonesia. Res. J. Pharm. Technol. 13, 6231–6237. https://doi.org/10.5958/0974-360X.2020.01086.0
Published
2024-09-25
How to Cite
Dewi, M. S., Riswanto, F. D. O., & Yuliani, S. H. (2024). Analytical Method Validation and Simultaneous Determination of Ketotifen Fumarate and Cyproheptadine Hydrochloride in Divided Powder by RP-HPLC Method. Indonesian Journal of Pharmacy, 35(3), 549-556. https://doi.org/10.22146/ijp.8308
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Short Communication
