All Title Author
Keywords Abstract

Quick Single Run Capillary Zone Electrophoresis Determination of Active Ingredients and Preservatives in Pharmaceutical Products

DOI: 10.4236/ajac.2013.43016, PP. 117-124

Keywords: Capillary Zone Electrophoresis, Nitrogenous Compound, Parabens, Pharmaceutical Analysis, Quality Control, Validation

Full-Text   Cite this paper   Add to My Lib


The paper deals with the development of a rapid and efficient Capillary Zone Electrophoresis (CZE) method for Quality Control analysis of pharmaceutical preparations containing antihistamines, decongestants, anticholinergic remedies and preservatives. Active ingredients of interest are: ChlorPheniramine Maleate (CPM), DiPhenhydramine Hydrochloride (DPH), Ephedrine hydrochloride (E), Isopropamide Iodide (II), Pheniramine Maleate (PM), Lidocaine hydrochloride (L), Tetracaine hydrochloride (T), Clopamide Hydrochloride (CH), DiHydroErgochristine (DHE), PhenylEphrine hydrochloride (PE) and Acetaminophen (A). Preservatives studied are: MethylParaben (MeP), EthylParaben (EtP), PropylParaben (PrP), ButylParaben (BuP), p-HydroxyBenzoic Acid (p-HBA). All these analytes were separated in a single run using 60 mM tetraborate buffer solution (TBS) pH = 9.2 as a BackGround Electrolyte (BGE) by using an uncoated fused silica capillary of I.D. = 50 mm and applying a voltage of 25 kV in the first part of the electropheretic run (up to 5.8 min) and 30 kV for the remaining time. The hydrodynamic pressurization of the inlet vial was 20 psi at 7.2 min. up to the end of analysis. Total separation time was of 7.5 min. The method was then successfully validated and applied to the simultaneous determination of active ingredients and preservatives. Good repeatability, linearity, and sensitivity were demonstrated. Precision of migration time (tm) was RSD% < 0.53% and of corrected peak area (Ac) was RSD% < 6.15%. The linearity evaluation gave 0.9928 < r2 < 1.000. LOD and LOQ, accuracy (recovery) and ruggedness were evaluated for each analyte demonstrating the good reliability of the method. Analyses of some pharmaceutical real samples were performed.


[1]  J. T. He, X. H. Zhao, Y. Chen and L. Fang, Chinese Journal of Pharmaceutical Analysis, Vol. 28, No. 1, 2008, pp. 143-145.
[2]  F. Buiarelli, F. Coccioli, R. Jasionowska and A. Terracciano, “Development and Validation of an MEKC Method for Determination of Nitrogen-Containing Drugs in Pharmaceutical Preparations,” Electrophoresis, Vol. 29, No. 17, 2008, pp. 3519-3523. doi:10.1002/elps.200700934
[3]  L. Zhang, Q. Hu, G. Chen and Y. Fang, “Simultaneous Determination of the Active Ingredients in Composite Pseudoephedrine Hydrochloride Tablets by Capillary Electrophoresis,” Analytical Chemistry Acta, Vol. 424, No. 2, 2000, pp. 257-262. doi:10.1016/S0003-2670(00)01117-X
[4]  B. Y. Yang, J. Y. Mo, X. Y. Yang and L. S. Wang, Sepu, Vol. 17, No. 5, 1999, pp. 477-479.
[5]  Z. P. Zang, X. G. Chen and Z. D. Hu, Journal of LiquidChromatography and Related Technologies, Vol. 20, No. 19, 1997, pp. 3225-3245.
[6]  W. P. Wang, Y. Li, Z. D. Hu and X. G. Chen, “Rapid and Ultrasensitive Determination of Ephedrine and Pseudoephedrine Derivatizated with 5-(4,6-Dichloro-S-triazin-2ylamino) Fluorescein by Micellar Electrokinetic Chromatography with Laser-Induced Fluorescence Detection,” Journal of Chromatography, Vol. 1102, No. 1-2, 2006, pp. 273-279. doi:10.1016/j.chroma.2005.10.015
[7]  J. P. Xie, J. Y. Zhang, J. Q. Liu, J. N. Tian, X. G. Chen and Z. D. Hu, Biomedical Chromatography, Vol. 19, No. 1, 2005, pp. 9-14.
[8]  J. P. Xie, J. Y. Zhang, J. Q. Liu, J. N. Tian, X. G. Chen and Z. D. Hu, “Micellar Electrokinetic Chromatography with Laser-Induced Fluorescence Detection for Sensitive Determination of Ephedrine and Pseudoephedrine,” Journal of Separation Science, Vol. 27, No. 14, 2004, pp. 1211-1214. doi:10.1002/jssc.200401756
[9]  M. R. Gomez, L. Sombra, R. A. Olsina, L. D. Martinez and M. F. Silva, “Development and Validation of a Capillary Electrophoresis Method for the Determination of Codeine, Diphenhydramine, Ephedrine and Noscapine in Pharmaceuticals,” Farmaco, Vol. 60, No. 1, 2005, pp. 85-90. doi:10.1016/j.farmac.2004.11.002
[10]  R. Gottardo, F. Bortolotti, G. De Paoli, J. Pascali, I. Miksik and F. Tagliaro, “Hair Analysis for Illicit Drugs by Using Capillary Zone Electrophoresis-Electrospray Ionization-Ion Trap Mass Spectrometry” Journal of Chromatography A, Vol. 1159, No. 1-2, 2007, pp. 185-189. doi:10.1016/j.chroma.2007.01.011
[11]  M. R. Gomez, R. A. Olsina, L. D. Martinez and M. F. Silva, Journal of Pharmaceutical and Biomedical Analysis, Vol. 30, No. 3, 30, 2002, pp. 791-799.
[12]  L. Suntornsuk, “Separation of Cold Medicine Ingredients by Capillary Electrophoresis,” Electrophoresis, Vol. 22, No. 1, 2001, pp. 139-143. doi:10.1002/1522-2683(200101)22:1<139::AID-ELPS139>3.0.CO;2-D
[13]  L. Suntornsuk, O. Pipitharome and P. Wilairat, Journal of Phamaceutical and Biomedical Analysis, Vol. 33, No. 3, 2003, pp. 441-449.
[14]  A. F. Marchesini, M. R. Williner, V. E. Mantovani, J. C. Robles and H. C. Goicoechea, “Separation and Determination of Pseudoephedrine, Dextromethorphan, Diphenhydramine and Chlorpheniramine in Cold Medicines by Nonaqueous Capillary Electrophoresis,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 39, No. 1-2, 2005, pp. 285-289. doi:10.1016/j.jpba.2005.02.032
[15]  M. D. Mertzman and J. P. Foley, “Comparison of Dodecoxycarbonylvaline Microemulsion, Solvent-Modified Micellar and Micellar Pseudostationary Phases for the Chiral Analysis of Pharmaceutical Compounds,” Electrophoresis, Vol. 26, No. 21, 2005, pp. 4153-4163. doi:10.1002/elps.200500351
[16]  H. Siren, T. Hiissa and Y. Min, Analyst, Vol. 125, No. 9, 2000, pp. 1561-1568.
[17]  F. Buiarelli, M. Franco, R. Jasionowska and G. Pelagalli, “CZE Separation of Nitrogenous Drugs in Cationic Form,” Analytical Methods, Vol. 6, No. 2, 2010, pp. 753-757. doi:10.1039/b9ay00277d
[18]  D. Ilko and U. Holzgrabe, “Influence of the Capillary Diameter on the Separation Efficiency and Sensitivity: A Systematic Approach,” Electrophoresis, Vol. 33, No. 11, 2012, pp. 1494-1498. doi:10.1002/elps.201100575
[19]  L. Nuñez, J. L. Tadeo, A. I. García-Valcárcel and E. Turiel, Journal of Chromatography A, Vol. 1214, 2008, p. 178.
[20]  M. R. Lee, C. Y. Lin, Z. G. Li and T. F. Tsai, “Simultaneous Analysis of Antioxidants and Preservatives in Cosmetics by Supercritical Fluid Extraction Combined with Liquid Chromatography-Mass Spectrometry,” Journal of Chromatography A, Vol. 1120, No. 1-2, 2006, pp. 244-251. doi:10.1016/j.chroma.2006.01.075
[21]  Q. Zhang, M. Lian, L. Liu and H. Cui, Analytica Chimica Acta, Vol. 537, 2005, p. 31.
[22]  A. Myint, Q. Zhang, L. Liu and H. Cui, Analytica Chimica Acta, Vol. 517, 2004, p. 119.
[23]  I. Garcia, M. C. Ortiz, L. Sarabia, C. Vilches and E. Gredilla, Journal of Chromatography A, Vol. 992, No. 11, 2003, pp. 1-2.
[24]  R. Hajkova, P. Solich, M. Pospisilova and J. Sicha, Analytica Chimica Acta, Vol. 467, No. 91, 2002, pp. 1-2.
[25]  M. Saraji and S. Mirmahdied, “Single-Drop Microextraction Followed by In-Syringe Derivatization and GC-MS Detection for the Determination of Parabens in Water and Cosmetic Products,” Journal of Separation Science, Vol. 32, No. 7, 2009, pp. 988-995. doi:10.1002/jssc.200800635
[26]  M. C. Pietrogrande and G. Basaglia, “GC-MS Analytical Methods for the Determination of Personal-Care Products in Water Matrices,” Trends in Analytical Chemistry, Vol. 26, No. 11, 2007, pp. 1086-1094. doi:10.1016/j.trac.2007.09.013
[27]  R. Driouich, T. Takayanagi, M. Oshima and S. Motomizu, Journal of Chromatography A, Vol. 903, No. 1-2, 2000, pp. 271-278.
[28]  B. Baalbaki, M. D. Blanchin and H. Fabre, Analytica Chimica Acta, Vol. 463, No. 1, 2002, p. 15.
[29]  H. Y. Huang, Y. C. Lai, C. W. Chiu and J. M. Yeh, Journal of Chromatography A, Vol. 993, No. 1-2, 2003, p. 153.
[30]  P. E. Mahuzier, K. D. Altria and B. J. Clark, “Selective and Quantitative Analysis of 4-Hydroxybenzoate Preservatives by Microemulsion Electrokinetic Chromatography,” Journal of Chromatography A, Vol. 924, No. 1-2, 2001, pp. 465-470. doi:10.1016/S0021-9673(01)00717-8
[31]  Y. H. Lin, S. S. Chou, F. Sheu and Y. T. Shyu, Journal of Chromatographic Science, Vol. 38, 2000, pp. 345-352.
[32]  R. A. Frazier, E. L. Inns, N. Dossi, J. M. Ames and H. E. Nursten, “Development of a Capillary Electrophoresis Method for the Simultaneous Analysis of Artificial Sweeteners, Preservatives and Colours in Soft Drinks,” Journal of Chromatography A, Vol. 876, No. 1-2, 2000, pp. 213-220. doi:10.1016/S0021-9673(00)00184-9
[33]  J. Safra and M. Psopisilová, “Separation and Determination of Ketoprofen, Methylparaben and Propylparaben in Pharmaceutical Preparation by Micellar Electrokinetic Chromatography,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 48, No. 2, 2008, pp. 452-455. doi:10.1016/j.jpba.2008.01.030
[34]  F. Han, Y. Z. He and C. Z. Yu, “On-Line Pretreatment and Determination of Parabens in Cosmetic Products by Combination of Flow Injection Analysis, Solid-Phase Extraction and Micellar Electrokinetic Chromatography,” Talanta, Vol. 74, No. 5, 2008, pp. 1371-1377. doi:10.1016/j.talanta.2007.09.007
[35]  S. He, Y. Zhao, Z. Zhu, H. Liu, M. Li, Y. Shao and Q. Zhuang, Talanta, Vol. 69, 2006, p. 166.
[36]  A. De Rossi and C. Desiderio, “Fast Capillary Electrochromatographic Analysis of Parabens and 4-Hydroxybenzoic Acid in Drugs and Cosmetics,” Electrophoresis, Vol. 23, No. 19, 2002, pp. 3410-3417. doi:10.1002/1522-2683(200210)23:19<3410::AID-ELPS3410>3.0.CO;2-I
[37]  E. Blanco, M. C. Casais, M. C. Mejuto and R. Cela, Electrophoresis, Vol. 29, 2008, p. 3229.
[38]  U. D. Uysal and T. Güray, “Determination of Parabens in Pharmaceutical and Cosmetic Products by Capillary Electrophoresis” Journal of Analytical Chemistry, Vol. 63, No. 10, 2008, pp. 982-986. doi:10.1134/S1061934808100109
[39]  E. J. Routledge, J. Parker, J. Odum, J. Ashby and J. P. Sumpter, “Some Alkyl Hydroxy Benzoate Preservatives (Parabens) Are Estrogenic,” Toxicology and Applied Pharmacology, Vol. 153, No. 1, 1998, pp. 12-19. doi:10.1006/taap.1998.8544
[40]  S. Oishi, “Effects of Propyl Paraben on the Male Reproductive System,” Food and Chemical Toxicology, Vol. 40, No. 12, 2002, pp. 1807-1813. doi:10.1016/S0278-6915(02)00204-1
[41]  R. Golden, J. Gandy and G. Vollmer, “A Review of the Endocrine Activity of Parabens and Implications for Potential Risks to Human Health,” Critical Reviews in Toxicology, Vol. 35, No. 5, 2005, pp. 435-458. doi:10.1080/10408440490920104
[42]  D. Philipa, P. Darbre and W. Harvey, “Paraben Esters: Review of Recent Studies of Endocrine Toxicity, Absorption, Esterase and Human Exposure, and Discussion of Potential Human Health Risks,” Journal of Applied Toxicology, Vol. 28, No. 5, 2008, pp. 561-578. doi:10.1002/jat.1358
[43]  European Economic Community (ECC) Instruction No. 93/95, Official Journal of the European Communities, Brussels, 1993, pp. 32-37.


comments powered by Disqus