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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Validated RP-LC Methods for Investigating the Degradation Behavior of Acefylline: Application for Analysis in Two Binary Mixtures

Author(s): Ola Mohamed EL-Houssini*, Nagwan Hamdi Zawilla and Mohammad Abdul-Azim Mohammad

Volume 17, Issue 6, 2021

Published on: 23 April, 2020

Page: [801 - 811] Pages: 11

DOI: 10.2174/1573412916999200423102505

Price: $65

Abstract

Background: Acefylline (Acef) is a derivative of theophylline that has bronchodilator effects. Two binary mixtures were marketed for Acef: Acefylline piperazine/ Phenobarbitone (Acef- P/Phen) and Acefylline heptaminol/ Cinnarizine (Acef-H/ Cinn). To our knowledge, none of the reported methods had the capacity to determine Acef in its binary mixture in the presence of its degradation products and potential impurity theophylline (Theo).

Methods: Two validated RP-LC methods were established for the determination of Acef-P/Phen and Acef-H/ Cinn, in the presence of Acef degradation products and its’ potential impurity Theo. A complete study of the forced acidic, alkaline, and oxidative degradation of Acef was presented. The methods were based on LC separation on RP C18 columns using isocratic and gradient elution for Acef-P /Phen and Acef-H /Cinn mixtures, respectively. Different chromatographic conditions were examined and optimized.

Results: Linear responses were attained over concentration ranges of 75-500/15-1000 μg/mL and 100- 1000 /50-500 μg/mL with mean percentage recoveries of (100.72±1.23)%/ (99.29±1.12)% and (100.44±1.27)%/ (99.01±0.97)% for Acef-P/Phen and Acef-H /Cinn, respectively. ICH guidelines were used for methods validation and all the parameters were found to be acceptable.

Conclusion: The methods showed to be accurate, precise, and specific for the analysis of Acef-P/Phen and Acef-H /Cinn in drug substance, drug product, and in laboratory prepared mixtures in the presence of Theo and up to 50% of degradation products. The structures of the main degradation products and the expected degradation pathway were suggested using the MS data.

Keywords: Acefylline (piperazine, heptaminol) (Acef-P) (Acef-H), phenobarbitone (Phen), cinnarizine (Cinn), theophylline (Theo), forced degradation study, stability indicating RP-LC.

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[1]
Maryadele, J. The Merch Index, 15th; Merck Research Laboratories: White House Station, . 2013.
[2]
Sweetman, S.C. Martindale: The Complete Drug Reference, 39th ed; The Pharmaceutical Press: London, 2017.
[3]
Kleeman, A.; Engels, J.; Kutscher, B.; Reichert, D. Pharmaceutical substances syntheses, patents, applications, 4th ed; Konrad Triltsch: Stuttgard, Germany, 2001.
[4]
EL-Gindy. A.; Emara, S.; Shaaban, H. Development and validation of chemometrics-assisted spectrophotometric and liquid chromatographic methods for the simultaneous determination of two multi components mixtures containing bronchodilator drugs. J. Pharm. Biomed. Anal., 2007, 19(43), 973-982.
[5]
The British Pharmacopoeia; Her Majesty's Stationary Office: London, UK, 2018.
[6]
The United States Pharmacopoeia (USP41), The United States Pharmacopoeial Convention, Rockville,,. 2018.
[7]
Somogyi, E.; Piotrowska, J. Acidimetric titration of medicines being salts of weak acids and determining the end-point based on the iodate(V)-iodide reaction. Acta Pol. Pharm., 2002, 59(3), 169-170.
[8]
Marciniec, B.; Ogrodowczyk, M. Direct determination of Theophylline Ephedrine hydrochloride and Phenobarbital in mixture., Chemica Analityczna (Warsaw Pol.),, 2002, 47, 283-288..
[9]
Ni, Y.N.; Wang, Y.R.; Kokot, S. Differential pulse stripping voltammetric determination of Paracetamol and Phenobarbital in pharmaceuticals assisted by chemometrics. Anal. Lett., 2004, 37, 3219-3235.
[http://dx.doi.org/10.1081/AL-200040332]
[10]
Boeris, M.S.; Luco, J.M.; Olsina, R.A. Simultaneous spectrophotometric determination of phenobarbital, phenytoin and methylphenobarbital in pharmaceutical preparations by using partial least-squares and principal component regression multivariate calibration. J. Pharm. Biomed. Anal., 2000, 24(2), 259-271.
[http://dx.doi.org/10.1016/S0731-7085(00)00416-7] [PMID: 11130205]
[11]
Salam, R.A.A.; Hadad, G.M.; Hameed, E.A.A. Simultaneous determination of two multi component mixtures containing Phenobarbitone and Ephedrine hydrochloride using HPLC and chemometric assisted spectrophotometric methods. J. Liq. Chromatogr. Relat. Technol., 2013, 36, 384-405.
[http://dx.doi.org/10.1080/10826076.2012.657735]
[12]
Saisho, K.; Tanaka, E.; Nakahara, Y. Hair analysis for pharmaceutical drugs. I. Effective extraction and determination of phenobarbital, phenytoin and their major metabolites in rat and human hair. Biol. Pharm. Bull., 2001, 24(1), 59-64.
[http://dx.doi.org/10.1248/bpb.24.59] [PMID: 11201247]
[13]
Mali, B.D.; Garad, M.V. Thin layer chromatographic detection of choral hydrate in an alcoholic beverage. J. Planar Chromatogr. Mod. TLC, 2005, 105, 397-399.
[http://dx.doi.org/10.1556/JPC.18.2005.5.13]
[14]
Mali, B.D.; Rathod, D.S.; Garad, M.V. Thin layer chromatographic determination of Diazepam, Phenobarbitone and Saccharin in toddy sample. J. Planar Chromatogr. Mod. TLC, 2005, 104, 330-332.
[http://dx.doi.org/10.1556/JPC.18.2005.4.16]
[15]
Meinitzer, A.; Kalcher, K.; Gartner, G.; Halwachs-Baumann, G.; März, W.; Stettin, M. Drugs and brain death diagnostics: determination of drugs capable of inducing EEG zero line. Clin. Chem. Lab. Med., 2008, 46(12), 1732-1738.
[http://dx.doi.org/10.1515/CCLM.2008.335] [PMID: 18973460]
[16]
Shabir, G.A.; Brahshaw, T.K.; Arian, S.A.; Shar, G.Q. A validated method for the simultaneous determination of a series of eight Barbiturates by RP-HPLC. J. Liq. Chromatogr. Relat. Technol., 2010, 33, 61-71.
[http://dx.doi.org/10.1080/10826070903430175]
[17]
Dalmora, S.L.; Sangoi, M.D.; Nogueira, D.R.; D’Avila, F.B.; Moreno, R.A.; Sverdloff, C.E.; De Oliveria, R.A.; Borges, N.C. Determination of phenobarbital in human plasma by a specific liquid chromatography method: application to a bioequivalence study. Quim. Nova, 2010, 33, 124-129.
[http://dx.doi.org/10.1590/S0100-40422010000100023]
[18]
Mhatre, P.R.; Gatkal, S.H.; Chopade, V.V.; Choudhari, P.D. Development and validation of stability indicating HPLC assay method for determination of phenobarbitone in bulk drug and tablet formulation. Int. J. Pharm. Sci. Res., 2013, 4, 1820-1826.
[19]
Ohyama, K.; Shirasawa, Y.; Wada, M.; Kishikawa, N.; Ohba, Y.; Nakashima, K.; Kuroda, N. Investigation of the novel mixed-mode stationary phase for capillary electrochromatography. I. Preparation and characterization of sulfonated naphthalimido-modified silyl silica gel. J. Chromatogr. A, 2004, 1042(1-2), 189-195.
[http://dx.doi.org/10.1016/j.chroma.2004.05.008] [PMID: 15296405]
[20]
Ohyama, K.; Wada, M.; Ohba, Y.; Fujishita, O.; Nakashima, K.; Kuroda, N. Rapid separation of barbiturates and benzodiazepines by capillary electrochromatography with 3-(1,8-naphthalimido)propyl-modified silyl silica gel. Biomed. Chromatogr., 2004, 18(6), 396-399.
[http://dx.doi.org/10.1002/bmc.346] [PMID: 15273980]
[21]
Issa, Y.M.; Youssef, A.F.A.; El-Hawary, W.A.; Abdel-Ghaffar, E.A. Spectrophotometric determination of cinnarizine through charge-transfer complex formation with polynitro compounds. Eur. Chem. Bull., 2013, 2, 507-515.
[22]
Abdelrahman, M.M. Simultaneous determination of Cinnarizine and Domperidone by area under curve and dual wavelength spectrophotometric methods. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2013, 113, 291-296.
[http://dx.doi.org/10.1016/j.saa.2013.04.120] [PMID: 23735208]
[23]
Tarkase, K.N.; Tarkase, M.K.; Dokhe, M.D.; Wagh, V.S. Development and validation of spectrophotometric method for simultaneous estimation of cinnarizine and domperidone maleate in pure and tablet dosage form. Int. J. Pharm. Sci. Res., 2012, 3, 2700-2704.
[24]
Lamie, N.T. Simultaneous determination of cinnarizine and dimenhydrinate in binary mixture using, first derivative of ratio spectra and bivariate spectrophotometric techniques., Analytical chemistry An Indian Journal, , 2014, 14, 93-99..
[25]
Abdelwahab, N.S.; Abdelrahman, M.M.; Salama, F.M.; Ahmed, A.B. Determination of dimenhydrinate and cinnarizine in combined dosage form in presence of cinnarizine impurity. Eur. J. Chem., 2015, 6, 475-481.
[http://dx.doi.org/10.5155/eurjchem.6.4.475-481.1324]
[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, 163-169.
[http://dx.doi.org/10.1016/j.bfopcu.2017.01.003]
[27]
Mahrouse, M.A. Validated chromatographic methods for simultaneous estimation of cinnarizine in binary mixture with domperidone and paracetamol in tablets. Curr. Pharmaceut Anal., 2019, 15(5), 429-438.
[http://dx.doi.org/ 10.2174/1573412914666180307154921]
[28]
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.
[PMID: 26354946]
[29]
Naga Sirisha, M.; Shanta Kumari, A. Validated RP-HPLC method for simultaneous estimation of cinnarizine and domperidone in bulk and pharmaceutical dosage form. J Pharm Sci Innov, 2013, 2, 46-50.
[http://dx.doi.org/10.7897/2277-4572.02218]
[30]
EL-Adl. S.M.; EL-Sadek, M.E.; Hasan, M.H. Exploring novel isocractic HPLC method for quantitative determination of cinnarizine and piracetam in their capsule preparations. J. App. Pharm., 2016, 8, 225.
[http://dx.doi.org/10.4172/1920-4159.1000225]
[31]
Heda, A.A.; Sonawane, A.R.; Naranje, G.H.; Puranik, P.K. A rapid determination of cinnarizine in bulk and pharmaceutical dosage form by LC. E-J. Chem., 2010, 7, 1080-1084.
[http://dx.doi.org/10.1155/2010/294096]
[32]
Puram, S.R.; Batheja, R.; Vivekanand, P.A. Rapid, sensitive method for the determination of cinnarizine in plasma by LC-MS/MS and it’s application to pharmacokinetic study. Int. J. Pharm. Sci. Res., 2017, 8, 5264-5269.
[33]
Abdelal, A.A.; Kitagawa, S.; Ohtani, H.; El-Enany, N.; Belal, F.; Walash, M.I. Method development and validation for the simultaneous determination of cinnarizine and co-formulated drugs in pharmaceutical preparations by capillary electrophoresis. J. Pharm. Biomed. Anal., 2008, 46(3), 491-497.
[http://dx.doi.org/10.1016/j.jpba.2007.11.012] [PMID: 18164891]
[34]
Ragab, G.; Saleh, H. EL-Henawee, M. ELsayed, O. A validated stability indicating RP-HPLC method for determination of phenobarbital and acefylline piperazine in bulk drug and combined dosage form. Eurasian J. Anal. Chem., 2016, 11, 197-210.
[35]
El-Gindy, A.; Emara, S.; Hadad, G.M. Determination of certain drugs in binary mixtures formulations by second derivative ratio spectrophotometry and LC. Farmaco, 2004, 59(9), 703-712.
[http://dx.doi.org/10.1016/j.farmac.2004.03.013] [PMID: 15337436]
[36]
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, 99-106.
[http://dx.doi.org/10.4137/ACI.S12478] [PMID: 24137049]
[37]
ICH Stability testing for new drug substance and products. International Conference on Harmonization for Registration of Pharmaceuticals for Human Use; Q1A(R2) Step4.pdf, ,. 2003.
[38]
ICH Stability testing for new drug substance and products. International Conference on Harmonization, IFPMA, Geneva, . 1993.
[39]
Bakshi, M.; Singh, B.; Singh, A.; Singh, S. International Conference on Harmonization. The ICH guidance in practice: stress degradation studies on ornidazole and development of a validated stability-indicating assay. J. Pharm. Biomed. Anal., 2001, 26(5-6), 891-897.
[http://dx.doi.org/10.1016/S0731-7085(01)00475-7] [PMID: 11600301]

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