Validated Chromatographic Methods for Simultaneous Estimation of Cinnarizine in Binary Mixture with Domperidone and Paracetamol in Tablets

Author(s): Marianne Alphonse Mahrouse, Asmaa Ahmed El-Zaher, Ahmed Mohammed Al-Ghani*.

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 5 , 2019

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Abstract:

Background: Cinnarizine, an antihistaminic drug, is commonly formulated in combination with domperidone and with paracetamol for treatment and prevention of motion sickness and migraine.

Objective: The aim of this work was to develop new, simple, precise and selective chromatographic methods (RP-HPLC and TLC-densitometric methods) for the determination of these drugs. These methods can be used as analytical tools in the routine examination in quality control laboratories.

Methods: The first method was RP-HPLC method, the separation was carried out on an Inertsil® ODS- 3V C18 column (250 mm × 4.6 mm, 5 µm) using a mobile phase composed of methanol: acetonitrile (45: 55, v/v) at a flow rate of 1 ml/min. The detection was carried out at 220 nm. The second method was a TLC-densitometric method where the studied components were separated using a developing system composed of toluene: ethyl acetate: methanol: triethylamine (5: 4.3: 0.7: 0.5, v/v/v/v) on TLC silica gel 60 F254 plates, followed by densitometric scanning at 270 nm.

Results: In RP-HPLC method, the peaks were sharp and well separated, the retention times were 5.25, 3.48 and 2.78 min, for cinnarizine, domperidone and paracetamol, respectively. Linearity was obtained over the concentration ranges 1-22, 0.75-16.5 and 25-550 µg/ml, for cinnarizine, domperidone and paracetamol, respectively. In TLC-densitometric method, good separation of spots and linear relationships were achieved over the concentration ranges of 0.2-2, 0.15-1.5 and 5-50 µg/spot, for cinnarizine, domperidone and paracetamol, respectively. Method validation was conducted according to ICH guidelines in terms of linearity, accuracy, selectivity, precision and robustness.

Conclusion: The developed methods were applied for the determination of the cited drugs in tablets containing binary drug mixtures. The methods are simple and precise and can be used for routine analysis of the labelled drugs in combined dosage forms in quality control laboratories.

Keywords: Cinnarizine, domperidone, paracetamol, RP-HPLC, TLC-densitometry, validation.

[1]
>1.J, M.; Heckelman, P.; Koch, C.; Roman, K. The Merck Index 14th Ed.Whitehouse Station, NJ: Merck; , 2006.
[2]
Sweetman, S.C. Martindale: The complete drug reference, 36th ed; Pharmaceutical press, 2011.
[3]
Rang, H.; Dale, M.; Ritter, J.; Moore, P. Churchill Livingstone. J. Pharmacol., 2003, 5, 374.
[4]
Cormie, P.; Nairn, M.; Welsh, J. Guidelines: Control of Pain in Adults with Cancer: Summary of SIGN Guidelines. Br. Med. J., 2008, 337(7678), 1106-1109.
[5]
Hundt, H.; Brown, L.; Clark, E. Determination of cinnarizine in plasma by high-performance liquid chromatography. J. Chromatogr. B Biomed. Sci. Appl., 1980, 183(3), 378-382.
[6]
Nitsche, V.; Mascher, H. Rapid high-performance liquid chromatographic assay of cinnarizine in human plasma. J. Chromatogr. B Biomed. Sci. Appl., 1982, 227(2), 521-525.
[7]
Rosseel, M.; Lefebvre, R. Sensitive determination of cinnarizine in human plasma by high performance liquid chromatography and fluorescence detection. Chromatographia, 1993, 36(1), 356-358.
[8]
Nowacka-Krukowska, H.; Rakowska, M.; Neubart, K.; Kobylińska, M. High-performance liquid chromatographic assay for cinnarizine in human plasma. Acta. Pol. Pharm-Dru Res., 2007, 64(5), 407-411.
[9]
Angelov, T. High-performance liquid chromatographic determination of cinnarizine in workplace air. Chromatographia, 2003, 58(7-8), 483-485.
[10]
Heda, A.; Sonawane, A.; Naranje, G.; Puranik, P. A rapid determination of cinnarizine in bulk and pharmaceutical dosage form by LC. J. Chem., 2010, 7(3), 1080-1084.
[11]
Shirode, A.R.; Ghuge, A.D.; Kadam, V.J. HPTLC method development and validation of cinnarizine in bulk and marketed formulation. Int. J. Pharm. Sci. Res., 2016, 7(6), 2416-2422.
[12]
Argekar, A.; Powar, S. Simultaneous HPTLC determination of cinnarizine and domperidone maleate in formulations. J. Planar. Chromat., 1999, 12(4), 272-274.
[13]
Argekar, A.; Shah, S. Simultaneous determination of cinnarizine and domepiridone maleate from tablet dosage form by reverse phase ion pair high performance liquid chromatography. J. Pharm. Biomed. Anal., 1999, 19(6), 813-817.
[14]
Bagade, S.; Walode, S.; Charde, M.; Tajne, M.; Kasture, A. Simultaneous HPTLC estimation of cinnarizine and domperidone in their combined dose tablet. Asian J. Chem., 2005, 17(2), 1116-1126.
[15]
Kumari, S.; Naga, S. Validated RP-HPLC method for simultaneous estimation of Cinnarizine and Domperidone in bulk and pharmaceutical dosage form. J. Pharm. Sci. Innov., 2013, 2(2), 46-50.
[16]
Prahalad, R.; Rao, R.N.; Konam, K.; Edara, S.R.; Rathna, T. Method development and validation for the simultaneous estimation Of domperidone maleate and cinnarizine in a pharmaceutical formulation by RP-HPLC method. Indo. Am. J. Pharm. Res., 2013, 3(10), 8111-8120.
[17]
Kalyankar, T.; Kulkarni, P.; Panchakshari, P.; Narute, A. Simultaneous RP-HPLC estimation of Cinnarizine and Domperidone in Tablet. Res. J. Pharm. Tech., 2014, 7(6), 650-654.
[18]
Chauhan, R.J.; Master, S.M.; Pasha, T.; Thakor, K.A.; Patel, P.U. Development and validation of RP-HPLC method for simultaneous estimation of cinnarizine and paracetamol in their pharmaceutical dosage form. Int. Bull. Drug Res., 2014, 4(7), 41-52.
[19]
Metwally, F.H.; Elzeany, B.; Darwish, H. New methods for determination of cinnarizine in mixture with piracetam by spectrodensitometry, spectrophotometry, and liquid chromatography. J. AOAC Int., 2005, 88(6), 1666-1676.
[20]
El-Houssini, O.M.; Zawilla, N.H.; Mohammad, M.A. Development and validation of RP-LC method for the determination of cinnarizine/piracetam and cinnarizine/heptaminol acefyllinate in presence of cinnarizine reported degradation products. Anal. Chem. Insights, 2013, 8(1), 99-106.
[21]
Navaneethan, G.; Karunakaran, K.; Elango, K. Stability indicating and simultaneous determination of cinnarizine and piracetam from capsule dosage form by reversed phase high performance liquid chromatography. Indian J. Chem. Technol., 2013, 20(9), 323-326.
[22]
SM. E.-A.; MH, H. Exploring novel isocractic HPLC method for quantitative determination of cinnarizine and piracetam in their capsule preparations. J Appl. Pharm., 2016, 8(3), 1-5.
[23]
Khushbu, S.; Pinkal, P. Development and validation of analytical method for simultaneous estimation of cinnarizine and dimenhydrinate in tablet dosage form. Int. J. Pharm. Sci. Res., 2014, 5(11), 4815-4819.
[24]
Lamie, N.T.; Monir, H.H. Simultaneous determination of cinnarizine and dimenhydrinate in binary mixture using chromatographic methods. J. Chromatogr. Sci., 2016, 54(1), 36-42.
[25]
El-Kafrawy, D.S.; Belal, T.S. Validated HPTLC method for the simultaneous determination of cinnarizine and dimenhydrinate in their combined dosage form. J. Associ. Arab Uni. Basic. Appl. Sci., 2016, 19(1), 15-22.
[26]
Ahmed, A.B.; Abdelwahab, N.S.; Abdelrahman, M.M.; Salama, F.M. Simultaneous determination of Dimenhydrinate, Cinnarizine and Cinnarizine impurity by TLC and HPLC chromatographic methods. Bull. Fac. Pharm. Cairo Univ., 2017, 55(1), 163-169.
[27]
Elkady, E.F.; Mahrouse, M.A. Reversed-phase ion-pair HPLC and TLC-densitometric methods for the simultaneous determination of ciprofloxacin hydrochloride and metronidazole in tablets. Chromatographia, 2011, 73(3-4), 297-305.
[28]
Branch, S.K. Guidelines from the international conference on harmonisation; ICH, 2005.
[29]
Convention, U.S.P. USP 32 NF 27: United States Pharmacopeia, National Formulary. Supplement 2. United States Pharmacopeial Convention. 2011.
[30]
G.B.S., Office U.K.S., '”British Pharmacopoeia; Stationery Office: London, 2016.


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Article Details

VOLUME: 15
ISSUE: 5
Year: 2019
Page: [429 - 438]
Pages: 10
DOI: 10.2174/1573412914666180307154921
Price: $58

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