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Current Analytical Chemistry

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ISSN (Print): 1573-4110
ISSN (Online): 1875-6727

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Research Article

A Friendly Environmental CE Method to Determine Doxycycline Hyclate in Suppositories and Application to Tablet Assay

Author(s): Ana P. Christ, Sulen L. Burin and Andréa I.H. Adams*

Volume 15, Issue 5, 2019

Page: [531 - 539] Pages: 9

DOI: 10.2174/1573411014666180131162033

Price: $65

Abstract

Background: The demand for green analytical methods is rising, mainly due its impact on the reduction of waste generation. The official method to assay Doxycycline Hiclate (DOXH) is HPLC, using an unusual column and a multi-component mobile phase.

Objective: To develop a capillary electrophoresis method (CZE) to assay DOXH in suppositories and tablets.

Methods: Doxycycline was analyzed in a CZE system using a fused silica capillary silica (effective length 40 cm), voltage 25kV, temperature 24°C, detection at 260 nm and hydrodynamic injection of 50mBar/5s. The electrolyte was a mixture of acetonitrile and aqueous solution composed of 25 mM sodium carbonate and 5mM EDTA, pH 10.6.

Results: The method was validated according to ICH requirements and DOXH detection was achieved at around 5 min. A linear relationship was observed in the range of 20 to 160 µg.mL-1, the method was precise, showing values of relative standard deviation below 2%. Accuracy was demonstrated by DOXH recovery values ranging from 98.0 to 102.0%, for all the formulations. The specificity was studied by the peak purity evaluation and by the good resolution between peaks of DOXH, degradation products and a related substance intentionally added to the sample solution. Robustness was evaluated by 23 full factorial design, and no effect on DOXH assay was observed under simultaneous variation in significant analytical parameters.

Conclusion: This simple and inexpensive method may be used to determine DOXH in suppositories as well tablets, under identical analytical conditions and can be a green alternative to the HPLC official method.

Keywords: Doxycycline hyclate, capillary electrophoresis, suppository, tablets, validation, factorial design.

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[1]
Bergogne-Bérézin, E.; Bryskier, A. The suppository form of antibiotic administration: Pharmacokinetics and clinical application. J. Antimicrob. Chemother., 1999, 43(2), 177-185.
[2]
Peters, R.K.; Schubert, T.; Clemmons, R.; Vickroy, T. Levetiracetam rectal administration in healthy dogs. J. Vet. Intern. Med., 2014, 28(2), 504-509.
[3]
Brewer, D.M.; Cerda-Gonzalez, S.; Dewey, C.W.; Boothe, D.; Van Horne, K. Pharmacokinetics of single-dose rectal zonisamide administration in normal dogs. J. Vet. Intern. Med., 2015, 29(2), 603-606.
[4]
Griffin, M.O.; Fricovsky, E.; Ceballos, G.; Villarreal, F. Tetracyclines : A pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am. J. Physiol. Cell Physiol., 2010, 299, 539-548.
[5]
Rinaldi, M.L. Therapeutic review: Doxycycline. J. Exot. Pet Med., 2014, 23(4), 415-417.
[6]
Jantratid, E.; Strauch, S.; Becker, C.; Dressman, J.B.; Amidon, G.L.; Junginger, H.E.; Kopp, S. Biowaiver monographs for immediate release solid oral dosage forms: Doxycycline hyclate. J. Pharm. Sci., 2010, 99(4), 1639-1653.
[7]
BP. British Pharmacopoeia; The Stationery Office, Ed.; London , 2007.
[8]
Brasil. Ministério da Agricultura e Pecuária - Coordenação de Fiscalização de Produtos Veterinários. 2014.
[9]
Maaland, M.G.; Papich, M.G.; Turnidge, J.; Guardabassi, L. Pharmacodynamics of doxycycline and tetracycline against staphylococcus pseudintermedius: Proposal of canine-specific breakpoints for doxycycline. J. Clin. Microbiol., 2013, 51(11), 3547-3554.
[10]
Smith, K.; Leyden, J.J. Safety of doxycycline and minocycline: A systematic review. Clin. Ther., 2005, 27(9), 1329-1342.
[11]
Gunn-Moore, D.A. Feline mycobacterial infections. Vet. J., 2014, 201(2), 230-238.
[12]
Papich, M.G. Antibiotic treatment of resistant infections in small animals. Vet. Clin. North Am. Small Anim. Pract., 2013, 43(5), 1091-1107.
[13]
USP 39. The United States Pharmacopeia, 39th ed; Rockville: The United States Pharmacopoeial Convention, 2016.
[14]
Skúlason, S.; Ingólfsson, E.; Kristmundsdóttir, T. Development of a simple HPLC method for separation of doxycycline and its degradation products. J. Pharm. Biomed. Anal., 2003, 33(4), 667-672.
[15]
Kogawa, A.C.; Salgado, H.R.N. Quantification of doxycycline hyclate in tablets by HPLC-UV method. J. Chromatogr. Sci., 2013, 51(10), 919-925.
[16]
Brum, L.; Uchoa, F.D.; Guterres, S.S.; Costa, T.D. Development and validation of LC-MS/MS method for the simultaneous determination of quinine and doxycycline in pharmaceutical formulations. J. Liq. Chromatogr. Relat. Technol., 2009, 32(18), 2699-2711.
[17]
Sunarić, S.M.; Denić, M.S.; Bojanić, Z.Ž.; Bojanić, V.V. HPLC method development for determination of doxycycline in human seminal fluid. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 939, 17-22.
[18]
Santos, M.D.F.; Vermeersch, H.; Remon, J.P.; Schelkens, M.; De Backer, P.; Ducatelle, R.; Haesebrouck, F. Validation of a high-performance liquid chromatographic method for the determination of doxycycline in turkey plasma. J. Chromatogr. B Biomed. Appl., 1996, 682(2), 301-308.
[19]
Krishna, A.C.; Sathiyaraj, M.; Saravanan, R.S.; Chelladurai, R.; Vignesh, R. A novel and rapid method to determine doxycycline in human plasma by liquid chromatography tandem mass spectrometry. Indian J. Pharm. Sci., 2012, 74(6), 541-548.
[20]
Gutiérrez, L.; Ocampo, L.; Espinosa, F.; Sumano, H. Pharmacokinetics of an injectable long-acting parenteral formulation of doxycycline hyclate in pigs. J. Vet. Pharmacol. Ther., 2014, 37(1), 83-89.
[21]
Riond, J-L.; Hedeen, K.M.; Tyczkowska, K.; Riviere, J.E. Determination of doxycycline in bovine tissues and body fluids by high performance liquid chromatography using photodiode array ultraviolet visible detection. J. Pharm. Sci., 1989, 78(1), 44-47.
[22]
Brum, L.; Leal, M.G.; Uchoa, F.D.; Kaiser, M.; Guterres, S.S.; Dalla Costa, T. Determination of quinine and doxycycline in rat plasma by LC-MS-MS: Application to a pharmacokinetic study. Chromatographia, 2011, 73(11-12), 1081-1088.
[23]
Schepdael, A.V.; Kibaya, R.; Roets, E.; Hoogmartens, J. Analysis of doxycycline by capillary electrophoresis. Chromatographia, 1995, 41(5/6), 367-369.
[24]
Gil, E.C.; Van Schepdael, A.; Roets, E.; Hoogmartens, J. Analysis of doxycycline by capillary electrophoresis. Method development and validation. J. Chromatogr. A, 2000, 895(1-2), 43-49.
[25]
Injac, R.; Kac, J.; Kreft, S.; Strukelj, B. Determination of doxycycline in pharmaceuticals and human urine by micellar electrokinetic capillary chromatography. Anal. Bioanal. Chem., 2007, 387(2), 695-701.
[26]
Altria, K.D.; Kelly, M.A.; Clark, B.J. Current applications in the analysis of pharmaceuticals by capillary electrophoresis. I. Trends Analyt. Chem., 1998, 17(4), 204-214.
[27]
Watson, D.G. Pharmaceutical analysis: A textbook for pharmacy students and pharmaceutical chemists, 2nd ed; Churchill Livingstone: Edinburgh, 1999.
[28]
ICH Expert Working Group Validation of analytical procedures: text and methodology Q2(R1). International Conference on Harmonisation of Techincal Requirements for Registration of Pharmaceuticals for Humans Use, 2005.
[29]
Shabir, G.A. Validation of high-performance liquid chromatography methods for pharmaceutical analysis. Understanding the differences and similarities between validation requirements of the US Food and Drug Administration, the US Pharmacopeia and the International Conf. J. Chromatogr. A, 2003, 987(1-2), 57-66.
[30]
Nemutlu, E.; Çelebier, M.; Uyar, B.; Altinöz, S. Validation of a rapid micellar electrokinetic capillary chromatographic method for the simultaneous determination of isoniazid and pyridoxine hydrochloride in pharmaceutical formulation. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 854(1-2), 35-42.
[31]
Mamani, M.C.V.; Farfán, J.A.; Reyes, F.G.R.; Rath, S. Simultaneous determination of tetracyclines in pharmaceuticals by CZE using experimental design. Talanta, 2006, 70(2), 236-243.
[32]
De Almeida, P.A.; Bhering, C.A.P.; Alves, M.C.; De Oliveira, M.A.L.; Raposo, N.R.B.; Ferreira, A.O.; Brandão, M.A.F. Development, optimization and validation of an HPLC-PDA method for quantification of taxifolin in the bark extract of Pinus pinaster. J. Braz. Chem. Soc., 2016, 27(9), 1648-1656.
[33]
Barden, A.T.; Piccoli, B.L.; Volpato, N.M.; Steppe, M. A simultaneous assay method using capillary zone electrophoresis for a fixed dose combination of vildagliptin and metformin hydrochloride in coated tablets. Anal. Methods, 2013, 5(20), 5701-5708.
[34]
Marcolino, A.I.P.; Sangoi, M.S.; Steppe, M.; Horn Adams, A.I.; Bueno Rolim, C.M. Determination of dronedarone in the pharmaceutical dosage form by a stability-indicating micellar electrokinetic chromatography method. Anal. Methods, 2013, 5(12), 3106-3113.
[35]
Kazsoki, A.; Fejos, I.; Sohajda, T.; Zhou, W.; Hu, W.; Szente, L.; Béni, S. Development and validation of a cyclodextrin-modified capillary electrophoresis method for the enantiomeric separation of vildagliptin enantiomers. Electrophoresis, 2016, 37(10), 1318-1325.
[36]
Teófilo, R.F.; Ferreira, M.M.C.; Quimiometria, I.I. Planilhas eletrônicas para cálculos de planejamentos experimentais, um tutorial. Quim. Nova, 2006, 29(2), 338-350.
[37]
Vander, H.Y.; Nijhuis, A.; Smeyers-verbeke, J.; Vandeginste, B.G.; Massart, D.L. Guidance for robustness / ruggedness tests in method validation. J. Pharm. Biomed. Anal., 2001, 24, 723-753.
[38]
Lenth, R.V. Quick and easy analysis for unreplicated factorials. Technometrics, 1989, 31, 469-473.
[39]
Brasil. Agência Nacional de Vigilância Sanitária, RDC n° 166, de 24 de julho de 2017 2017.

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