Skip to content
2000
image of Advancements in Analytical Techniques for Preservative Identification in Pharmaceuticals

Abstract

Introduction

Preservatives are widely used chemical agents that inhibit microbial growth and extend the shelf life of food and pharmaceutical products. However, growing concerns over the potential adverse effects of synthetic preservatives, such as parabens and benzoates, have emphasized the need for precise and reliable analytical methods for their detection and quantification.

Methods

This review evaluates and compares various analytical techniques employed for preservative analysis in pharmaceutical formulations, including chromatographic (HPLC, GC-MS), spectroscopic (UV-Vis), electrophoretic (CE), and electrochemical methods. Parameters such as sensitivity, accuracy, separation efficiency, and applicability in complex matrices were assessed across different techniques.

Results

High-performance liquid chromatography (HPLC) demonstrated superior sensitivity with detection limits as low as 0.01 µg/mL and excellent linearity (R2 > 0.999), making it the most widely adopted method. Capillary electrophoresis (CE) provided rapid analysis within 10 minutes and high recovery rates (>98%). UV-Vis spectroscopy, although economical, faced challenges in analyzing complex samples due to spectral overlapping. Gas chromatography–mass spectrometry (GC-MS) excelled in identifying volatile preservatives through enhanced structural elucidation.

Discussion

HPLC emerged as the gold standard for routine preservative analysis due to its high precision (RSD < 2%), versatility, and ability to quantify multiple preservatives concurrently. While GC-MS offers detailed structural insight, it is more suited for specific applications. Emerging methods like UPLC and CE are gaining attention for their speed and reduced solvent usage, aligning with green analytical chemistry principles.

Conclusion

Robust and sensitive analytical techniques are essential for the accurate determination of preservatives to ensure pharmaceutical safety and regulatory compliance. Continued innovation and optimization in analytical methodologies enhances the reliability of preservative monitoring and contributes significantly to public health risk assessment.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdrr/10.2174/0125899775390873250721162514
2025-09-02
2025-10-19

  • From This Site

    /content/journals/cdrr/10.2174/0125899775390873250721162514
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Fahelelbom K.M. El-Shabrawy Y. Analysis of preservatives in pharmaceutical products. Pharm. Rev. 2007 5 1 1 55 18055507
    [Google Scholar]
  2. Ligthart J.J. NGO initiatives in the eu – identifying substances of very high concern (svhcs) and driving safer chemical substitutes in response to reACH. Chemical Alternatives Assessments 2013 36 230 255 10.1039/9781849737234‑00230
    [Google Scholar]
  3. Czarczyńska-Goślińska B. Zgoła-Grześkowiak A. Jeszka-Skowron M. Frankowski R. Grześkowiak T. Detection of bisphenol A, cumylphenol and parabens in surface waters of Greater Poland Voivodeship. J. Environ. Manage. 2017 204 Pt 1 50 60 10.1016/j.jenvman.2017.08.034 28854378
    [Google Scholar]
  4. Petric Z. Ružić J. Žuntar I. The controversies of parabens – an overview nowadays. Acta Pharm. 2021 71 1 17 32 10.2478/acph‑2021‑0001 32697748
    [Google Scholar]
  5. Porta N. Roncaglioni A. Marzo M. Benfenati E. QSAR methods to screen endocrine disruptors. Nucl. Receptor Res. 2016 3
    [Google Scholar]
  6. Frankowski R. Zgoła-Grześkowiak A. Smułek W. Grześkowiak T. Removal of bisphenol A and its potential substitutes by biodegradation. Appl. Biochem. Biotechnol. 2020 191 3 1100 1110 10.1007/s12010‑020‑03247‑4 31960364
    [Google Scholar]
  7. Anand S.P. Sati N. Artificial preservatives and their harmful effects: Looking toward nature for safer alternatives. Int. J. Pharm. Sci. Res. 2013 4 7 2496 2501
    [Google Scholar]
  8. Shaikh S.M. Doijad R.C. Shete A.S. Sankpal P.S. A review on: Preservatives used in pharmaceuticals and impacts on health. PharmaTutor 2016 4 5 25 34
    [Google Scholar]
  9. De Villiers M.M. Antimicrobial preservatives. In: A Practical Guide to Contemporary Pharmacy Practice. 3rd ed. Philadelphia, PA 2009 203 5
    [Google Scholar]
  10. de Villiers M. Surfactants and emulsifying agents. In: Thompson JE, Ed. A Practical Guide to Contemporary Pharmacy Practice. Thompson J.E. Philadelphia Lippincott Williams and Wilkins 2009 251
    [Google Scholar]
  11. Arrioja-Bretón D. Mani-López E. Palou E. López-Malo A. Antimicrobial activity and storage stability of cell-free supernatants from lactic acid bacteria and their applications with fresh beef. Food Control 2020 115 107286 10.1016/j.foodcont.2020.107286
    [Google Scholar]
  12. Kumar A. Singh P. Gupta V. Prakash B. Application of nanotechnology to boost the functional and preservative properties of essential oils. In: Functional and preservative properties of phytochemicals. Academic Press 2020 241 267 10.1016/B978‑0‑12‑818593‑3.00008‑7
    [Google Scholar]
  13. Rathee P. Sehrawat R. Rathee P. Polyphenols: Natural preservatives with promising applications in food, cosmetics and pharma industries; problems and toxicity associated with synthetic preservatives; impact of misleading advertisements; recent trends in preservation and legislation. Materials 2023 16 13 4793 10.3390/ma16134793 37445107
    [Google Scholar]
  14. de Villiers A. Alberts P. Tredoux A.G.J. Nieuwoudt H.H. Analytical techniques for wine analysis: An African perspective; a review. Anal. Chim. Acta 2012 730 2 23 10.1016/j.aca.2011.11.064 22632040
    [Google Scholar]
  15. Lu L. Xiong W. Li X. Determination of the migration of eight parabens from antibacterial plastic packaging by liquid chromatography-electrospray ionization-tandem mass spectrometry. Anal. Methods 2014 6 7 2096 2101 10.1039/c3ay42080a
    [Google Scholar]
  16. Tripathi K.D. Essentials of medical pharmacology. JP Medical Ltd 2013
    [Google Scholar]
  17. Mehta S.K. Gowder S.J. Members of antioxidant machinery and their functions. In: Basic Principles and Clinical Significance of Oxidative Stress. InTech 2015 10.5772/61884
    [Google Scholar]
  18. Siegert W. Boosting the antimicrobial efficiency of multifunctional additives by chelating agents. Int J Appl Sci 2014 140 1 6
    [Google Scholar]
  19. Kameyama Y. Matsuhama M. Mizumaru C. Saito R. Ando T. Miyazaki S. Comparative study of pharmacopoeias in Japan, Europe, and the United States: Toward the further convergence of international pharmacopoeial standards. Chem Pharm 2019 67 12 1301 1313 10.1248/cpb.c19‑00621 31787657
    [Google Scholar]
  20. Sarma N. Upton R. Rose U. Pharmacopeial standards for the quality control of botanical dietary supplements in the United States. J. Diet. Suppl. 2023 20 3 485 504 10.1080/19390211.2021.1990171 34699287
    [Google Scholar]
  21. Ma C. Oketch-Rabah H. Kim N.C. Quality specifications for articles of botanical origin from the United States Pharmacopeia. Phytomedicine 2018 45 105 119 10.1016/j.phymed.2018.04.014 29778318
    [Google Scholar]
  22. Pinheiro F.C. Aguirre M.Á. Nóbrega J.A. Canals A. Dispersive liquid–liquid microextraction of Cd, Hg and Pb from medicines prior to ICP OES determination according to the United States Pharmacopeia. Anal. Methods 2021 13 46 5670 5678 10.1039/D1AY01566D 34792519
    [Google Scholar]
  23. Wallack G. Rethinking FDA’S regulation of cosmetics. Harv. J. Legis. 2019 56 311
    [Google Scholar]
  24. Pratiwi R. Auliya As N.N. Yusar R.F. Shofwan A.A.A. Analysis of prohibited and restricted ingredients in cosmetics. Cosmetics 2022 9 4 87 10.3390/cosmetics9040087
    [Google Scholar]
  25. Watnick V.J. The missing link: US regulation of consumer cosmetic products to protect human health and the environment. Pace Envtl. L. Rev. 2014 31 3 595 10.58948/0738‑6206.1749
    [Google Scholar]
  26. Dorato S. General concepts: Current legislation on cosmetics in various countries. In: Analysis of Cosmetic Products. Elsevier 2018 3 37
    [Google Scholar]
  27. Milstein S.R. Jurkiewicz M. Ciarlo G. Report for the international cooperation on cosmetics regulation. In:
    [Google Scholar]
  28. Sharmeen J. Mahomoodally F. Zengin G. Maggi F. Essential oils as natural sources of fragrance compounds for cosmetics and cosmeceuticals. Molecules 2021 26 3 666 10.3390/molecules26030666 33514008
    [Google Scholar]
  29. Ahuja A. Potanin A. Rheological and sensory properties of toothpastes. Rheol. Acta 2018 57 6-7 459 471 10.1007/s00397‑018‑1090‑z
    [Google Scholar]
  30. Ahuja V. Macho M. Ewe D. Singh M. Saha S. Saurav K. Biological and pharmacological potential of xylitol: A molecular insight of unique metabolism. Foods 2020 9 11 1592 10.3390/foods9111592 33147854
    [Google Scholar]
  31. Correa G. Canavez A. Isaac V. Lorencini M. Schuck D. Preservation of personal care and cosmetic products: Effectiveness and safety during the covid-19 pandemic. J. Cosmet. Sci. 2022 73 2
    [Google Scholar]
  32. Ahuja J.K.C. Li Y. Nguyen Q. Pehrsson P.R. Characterizing ingredients in commercially packaged baked products sold in the U.S.: An application of IngID. J. Food Compos. Anal. 2022 114 104830 10.1016/j.jfca.2022.104830
    [Google Scholar]
  33. Loganathan B.G. Ahuja S. Subedi B. Synthetic organic chemical pollutants in water: Origin, distribution, and implications for human exposure and health. In: Contaminants in our water: Identification and remediation methods. American Chemical Society 2020 13 39
    [Google Scholar]
  34. Ahuja A. Pappas I. Potanin A. Relation between structure and stability of toothpaste with two-step yielding. Rheol. Acta 2020 59 3 133 145 10.1007/s00397‑019‑01183‑7
    [Google Scholar]
  35. Chaudhari P.R. Tamrakar N. Singh L. Tandon A. Sharma D. Rice nutritional and medicinal properties: A review article. J. Pharmacogn. Phytochem. 2018 7 2 150 156
    [Google Scholar]
  36. Wang J. Liu Y. Kam W.R. Li Y. Sullivan D.A. Toxicity of the cosmetic preservatives parabens, phenoxyethanol and chlorphenesin on human meibomian gland epithelial cells. Exp. Eye Res. 2020 196 108057 10.1016/j.exer.2020.108057 32387382
    [Google Scholar]
  37. Assaf Vandecasteele H. Gautier F. Tourneix F. Vliet E. Bury D. Alépée N. Next generation risk assessment for skin sensitisation: A case study with propyl paraben. Regul. Toxicol. Pharmacol. 2021 123 104936 10.1016/j.yrtph.2021.104936 33905779
    [Google Scholar]
  38. Shank PD Slaga TJ Snyder PW Amended safety assessment of quaternium-18 and quaternium-18 bentonite as used in cosmetics.
    [Google Scholar]
  39. Kim J.Y. Im J.E. Lee J.D. Kim K.B. Analytical method development and percutaneous absorption of propylidene phthalide, a cosmetic ingredient. J. Toxicol. Environ. Health A 2021 84 20 811 820 10.1080/15287394.2021.1944941 34187329
    [Google Scholar]
  40. Gui M. Zhang D. Tran J.M. Reeder M.J. The hoax of clean beauty and associated allergens. Curr. Dermatol. Rep. 2023 12 4 269 278 10.1007/s13671‑023‑00399‑4
    [Google Scholar]
  41. Neri I. Laneri S. Di Lorenzo R. Dini I. Russo G. Grumetto L. Parabens permeation through biological membranes: A comparative study using Franz cell diffusion system and biomimetic liquid chromatography. Molecules 2022 27 13 4263 10.3390/molecules27134263 35807508
    [Google Scholar]
  42. Lai N.Z. The effects of propylparaben on preimplantation embryo development. In: Doctoral dissertation.
    [Google Scholar]
  43. Şenkuytu E. Kızılkaya P. Ölçer Z. Electrophoresis and biosensor-based DNA interaction analysis of the first paraben derivatives of spermine-bridged cyclotriphosphazenes. Inorg. Chem. 2020 59 4 2288 2298 10.1021/acs.inorgchem.9b03031 31986027
    [Google Scholar]
  44. Kaur R. Kaur L. Encapsulated natural antimicrobials: A promising way to reduce microbial growth in different food systems. Food Control 2021 123 107678 10.1016/j.foodcont.2020.107678
    [Google Scholar]
  45. Kaur J. Gill G.S. Jeet K. Applications of carbon nanotubes in drug delivery: A comprehensive review. In: Characterization and Biology of Nanomaterials for Drug Delivery. Elsevier 2019 113 135 9780128140314 10.1016/B978‑0‑12‑814031‑4.00005‑2
    [Google Scholar]
  46. Kaur J. Kaur R. p -Coumaric Acid: A naturally occurring chemical with potential therapeutic applications. Curr. Org. Chem. 2022 26 14 1333 1349 10.2174/1385272826666221012145959
    [Google Scholar]
  47. Kaur J. Sarma A.K. Jha M.K. Gera P. Valorisation of crude glycerol to value-added products: Perspectives of process technology, economics and environmental issues. Biotechnol. Rep. 2020 27 e00487 10.1016/j.btre.2020.e00487 32642454
    [Google Scholar]
  48. Sharma P. Kaur J. Sharma G. Kashyap P. Plant derived antimicrobial peptides: Mechanism of target, isolation techniques, sources and pharmaceutical applications. J. Food Biochem. 2022 46 10 e14348 10.1111/jfbc.14348 35945701
    [Google Scholar]
  49. Rimal A Thagunna B Kaur J AN An overview of sugarcane: Production, harvesting, benefits, preservation, and value-added products.
    [Google Scholar]
  50. Gray J.A. Chandry P.S. Kaur M. Kocharunchitt C. Bowman J.P. Fox E.M. Novel biocontrol methods for Listeria monocytogenes biofilms in food production facilities. Front. Microbiol. 2018 9 605 10.3389/fmicb.2018.00605 29666613
    [Google Scholar]
  51. Sirilun S. Chaiyasut C. Sivamaruthi B.S. Peerajan S. Kumar N. Periyanaina K. Phenethyl alcohol is an effective non-traditional preservative agent for cosmetic preparations. Asian J. Pharm. Clin. Res. 2017 10 8 129 133 10.22159/ajpcr.2017.v10i8.18572
    [Google Scholar]
  52. Castanedo-Tardana M.P. Zug K.A. Methylisothiazolinone. Dermatitis 2013 24 1 2 6 10.1097/DER.0b013e31827edc73 23340392
    [Google Scholar]
  53. Jennings M.C. Tilley D.H. Ballard S.B. Case–Case Analysis Using 7 Years of Travelers’ Diarrhea Surveillance Data: Preventive and Travel Medicine Applications in Cusco, Peru. Am. J. Trop. Med. Hyg. 2017 96 5 1097 1106 10.4269/ajtmh.16‑0633 28167602
    [Google Scholar]
  54. Geis P.A. Preservatives and Preservation. In: Cosmetic Microbiology: A Practical Approach. 2020 6 15
    [Google Scholar]
  55. Herman A. Antimicrobial ingredients as preservative booster and components of self-preserving cosmetic products. Curr. Microbiol. 2019 76 6 744 754 10.1007/s00284‑018‑1492‑2 29651551
    [Google Scholar]
  56. Krueger K.L. Ungar P.S. Guatelli-Steinberg D. Anterior dental microwear textures show habitat-driven variability in Neandertal behavior. J. Hum. Evol. 2017 105 13 23 10.1016/j.jhevol.2017.01.004 28366197
    [Google Scholar]
  57. Choubey S. Godbole S. Methods for evaluation of microbiological safety, guidelines governing the quality and survey on microbial contamination of commercial cosmetic products. World Journal of Pharmaceutical and Medical Research 2017 3 85 94
    [Google Scholar]
  58. Rabiu F. Forsey P. Patel S. Preservatives can produce harmful effects in paediatric drug preparations. Pharm. Pract. 2004 14 101 108
    [Google Scholar]
  59. Kumar S. Mathkar S. Romero C. Rustum A.M. Development and validation of a single RP-HPLC assay method for analysis of bulk raw material batches of four parabens that are widely used as preservatives in pharmaceutical and cosmetic products. J. Chromatogr. Sci. 2011 49 5 405 411 10.1093/chromsci/49.5.405 21549034
    [Google Scholar]
  60. Castro-Gómez P. Montero O. Fontecha J. In-depth lipidomic analysis of molecular species of triacylglycerides, diacylglycerides, glycerophospholipids, and sphingolipids of buttermilk by GC-MS/FID, HPLC-ELSD, and UPLC-QToF-MS. Int. J. Mol. Sci. 2017 18 3 605 10.3390/ijms18030605 28287421
    [Google Scholar]
  61. Golzari Aqda T. Behkami S. Raoofi M. Bagheri H. Graphene oxide-starch-based micro-solid phase extraction of antibiotic residues from milk samples. J. Chromatogr. A 2019 1591 7 14 10.1016/j.chroma.2018.11.069 30503697
    [Google Scholar]
  62. Steinmann D. Ganzera M. Recent advances on HPLC/MS in medicinal plant analysis. J. Pharm. Biomed. Anal. 2011 55 4 744 757 10.1016/j.jpba.2010.11.015 21131153
    [Google Scholar]
  63. Barny L.A. Liquid chromatography-mass spectrometry (lc-ms) applications in chemical ecology: Analysis of retronecine-type pyrrolizidine alkaloids and natural products associated with amphibian skin secretions. Doctoral dissertation
    [Google Scholar]
  64. Sereshti H. Semnani Jazani S. Nouri N. Shams G. Dispersive liquid–liquid microextraction based on hydrophobic deep eutectic solvents: Application for tetracyclines monitoring in milk. Microchem. J. 2020 158 105269 10.1016/j.microc.2020.105269
    [Google Scholar]
  65. Šrajer Gajdošik M. Andjelković U. Gašo-Sokač D. Proteomic analysis of food borne pathogens following the mode of action of the disinfectants based on pyridoxal oxime derivatives. Food Res. Int. 2017 99 Pt 1 560 570 10.1016/j.foodres.2017.06.016 28784517
    [Google Scholar]
  66. Raje M.R. Knott K. Kharel Y. Bissel P. Lynch K.R. Santos W.L. Design, synthesis and biological activity of sphingosine kinase 2 selective inhibitors. Bioorg. Med. Chem. 2012 20 1 183 194 10.1016/j.bmc.2011.11.011 22137932
    [Google Scholar]
  67. Wang Y. Li J. Xu Z. The formation process of green substances in Chrysanthemum morifolium tea. Food Chem. 2020 326 127028 10.1016/j.foodchem.2020.127028 32428857
    [Google Scholar]
  68. Goswami J. Different separation or experimental techniques for clinical chromatography: Small review. J. Chromatogr. Sep. Tech. 2015 6 7 1 10.4172/2157‑7064.1000297
    [Google Scholar]
  69. De Saint Jean M. Brignole F. Bringuier A.F. Bauchet A. Feldmann G. Baudouin C. Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells. Invest. Ophthalmol. Vis. Sci. 1999 40 3 619 630 10067965
    [Google Scholar]
  70. Lunestad B.T. Møretrø T. Hegstad K. Chlorhexidine compounds in cosmetic products. Risk assessment of antimicrobial and antibiotic resistance development in microorganisms. Nor Sci Comm Food Saf 2010
    [Google Scholar]
  71. Rasmussen C.D. Nielsen H.B. Andersen J.E. Analysis of the purity of cetrimide by titrations. PDA J. Pharm. Sci. Technol. 2006 60 2 104 110 16696193
    [Google Scholar]
  72. Ali Khan J. Muhammad S. Iqbal Z. Evaluation of commonly used preservatives in various analgesic suspensions through HPLC and Microbial Assay. J. Liq. Chromatogr. Relat. Technol. 2012 35 13 1853 1870 10.1080/10826076.2011.627606
    [Google Scholar]
  73. Singh J.P. Thakur S.N. Laser-induced breakdown spectroscopy. Elsevier 2020
    [Google Scholar]
  74. Singh V.K. Rai A.K. Prospects for laser-induced breakdown spectroscopy for biomedical applications: A review. Lasers Med. Sci. 2011 26 5 673 687 10.1007/s10103‑011‑0921‑2 21533560
    [Google Scholar]
  75. Thakur A.K. Choudhary R.B. Majumder M. Majhi M. Fairly improved pseudocapacitance of PTP/PANI/TiO2 nanohybrid composite electrode material for supercapacitor applications. Ionics 2018 24 1 257 268 10.1007/s11581‑017‑2183‑x
    [Google Scholar]
  76. Savaliya U. Tarai D.K. Sarkar S. Kirtane S.R. RP-HPLC method development and validation for the determination of fimasartan and hydrochlorothiazide. Pharma Sci. Monitor 2023 14 2
    [Google Scholar]
  77. Thakur V.K. Thakur M.K. Recent advances in graft copolymerization and applications of chitosan. Review 2014 2 12 2637 2652 10.1021/sc500634p
    [Google Scholar]
  78. Dhahir S.A. Hussein H.J. Spectrophotometric determination of methyl paraben in pure and pharmaceutical oral solution. Advances in Natural Science 2013 6 4 69 74
    [Google Scholar]
  79. Baranowska I. Wojciechowska I. Solarz N. Krutysza E. Determination of preservatives in cosmetics, cleaning agents and pharmaceuticals using fast liquid chromatography. J. Chromatogr. Sci. 2014 52 1 88 94 10.1093/chromsci/bms210 23324734
    [Google Scholar]
  80. Santoni G. Medica A. Gratteri P. Furlanetto S. Pinzauti S. High-performance liquid chromatographic determination of benzalkonium and naphazoline or tetrahydrozoline in nasal and ophthalmic solutions. Farmaco 1994 40 11 751 754
    [Google Scholar]
  81. Bernal J.L. del Nozal M.J. Martín M.T. Diez-Masa J.C. Cifuentes A. Quantitation of active ingredients and excipients in nasal sprays by high-performance liquid chromatography, capillary electrophoresis and UV spectroscopy. J. Chromatogr. A 1998 823 1-2 423 431 10.1016/S0021‑9673(98)00451‑8 9818419
    [Google Scholar]
  82. Toomey A.B. Dalrymple D.M. Jasperse J.L. Manning M.M. Schulz M.V. Analysis of quaternary ammonium compounds by high performance liquid chromatography with evaporative light scattering detection. J. Liq. Chromatogr. Relat. Technol. 1997 20 7 1037 1047 10.1080/10826079708010956
    [Google Scholar]
  83. G Singh S Singh S. Simultaneous determination of preservatives (methyl paraben and propyl paraben) in sucralfate suspension using high performance liquid chromatography. J. Chem. 2011 8 340 346 10.1155/2011/360431
    [Google Scholar]
  84. Radus T.P. Gyr G. Determination of antimicrobial preservatives in pharmaceutical formulations using reverse-phase liquid chromatography. J. Pharm. Sci. 1983 72 3 221 224 10.1002/jps.2600720305 6842372
    [Google Scholar]
  85. Antakli S. Kabani R. Shawa D. Determination of preservative parabens in oral and injection formulations by HPLC. Asian J. Chem. 2013 25 2 1123 1128 10.14233/ajchem.2013.13627
    [Google Scholar]
  86. Quarry M.A. Sebastian D.S. Williams R.C. Determination of nalbuphine hydrochloride, methylparaben, and propylparaben in nalbuphine hydrochloride injection by high performance liquid chromatography. Chromatographia 1998 47 9-10 515 522 10.1007/BF02467488
    [Google Scholar]
  87. Sudha T. Manthena K. Ravikumar V.R. Ganesan V. High performance liquid chromatographic method for the determination of ambroxol hydrochloride in presence of antimicrobial preservatives in oral liquid formulation. Bangladesh Pharm Journal 2015 18 1 8 14 10.3329/bpj.v18i1.23505
    [Google Scholar]
  88. Belgaied J.E. Trabelsi H. Determination of cisapride, its oxidation product, propyl and butyl parabens in pharmaceutical dosage form by reversed-phase liquid chromatography. J. Pharm. Biomed. Anal. 2003 33 5 991 998 10.1016/S0731‑7085(03)00421‑7 14656590
    [Google Scholar]
  89. Ali M.S. Chaudhary R.S. Takieddin M.A. Simultaneous determination of metronidazole benzoate, methylparaben, and propylparaben by high-performance liquid chromatography. Drug Dev. Ind. Pharm. 1999 25 10 1143 1147 10.1081/DDC‑100102281 10529896
    [Google Scholar]
  90. Kollmorgen D. Kraut B. Determination of methylparaben, propylparaben and chlorpromazine in chlorpromazine hydrochloride oral solution by high-performance liquid chromatography. J. Chromatogr., Biomed. Appl. 1998 707 1-2 181 187 10.1016/S0378‑4347(97)00618‑X 9613948
    [Google Scholar]
  91. Ivković B. Brborić J. Dobričić V. Čudina O. Development and validation of a new isocratic RP-HPLC method for simultaneous determination of sodium metabisulfite and sodium benzoate in pharmaceutical formulation. Acta Chromatogr. 2019 31 2 133 137 10.1556/1326.2017.00404
    [Google Scholar]
  92. Elbagary R.I. Elkady E.F. Tammam M.H. Elmaaty A.A. Simultaneous estimation of terconazole and benzoic acid in bulk and creams using rp-hplc, derivative spectrophotometry and chemometric techniques. J. Chem. Pharm. Res. 2017 9 3 280 291
    [Google Scholar]
  93. Dinç Zor Ş. Aşçı B. Aksu Dönmez Ö. Yıldırım Küçükkaraca D. Simultaneous determination of potassium sorbate, sodium benzoate, quinoline yellow and sunset yellow in lemonades and lemon sauces by HPLC using experimental design. J. Chromatogr. Sci. 2016 54 6 952 957 10.1093/chromsci/bmw027 26951541
    [Google Scholar]
  94. Hasan N. Chaiharn M. Shah S.N. Khalid H. Jabbar A. Simultaneous determination of nsaid and antimicrobial preservatives using validated rp-hplc method: An application in pharmaceutical and clinical laboratories. Pharm. Anal. Acta 2013 4 8 263 269 10.4172/2153‑2435.1000263
    [Google Scholar]
  95. Shabir G.A. Development and validation of a stability-indicating LC method for the determination of domperidone, sorbic acid, and propylparaben in pharmaceutical formulations. J. Liq. Chromatogr. Relat. Technol. 2010 33 20 1802 1813 10.1080/10826076.2010.532702
    [Google Scholar]
  96. Shabir G.A. Method development and validation of preservatives determination (benzyl alcohol, ethylene glycol monophenyl ether, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, and butyl hydroxybenzoate) using HPLC. J. Liq. Chromatogr. Relat. Technol. 2007 30 13 1951 1962 10.1080/10826070701386553
    [Google Scholar]
  97. Shen Y. Xu S. Wang S. Tu J. Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography. J. Zhejiang Univ. Sci. B 2009 10 12 877 882 10.1631/jzus.B0920229 19946951
    [Google Scholar]
  98. AlAani H AlNukkary Y Determination of benzalkonium chloride in ophthalmic solutions by stability-indicating HPLC method: Application to a stability study. J Appl Pharm Sci 2016 May 28 6 5 080 9 10.7324/JAPS.2016.60513
    [Google Scholar]
  99. Mehta J. Patel V. Kshatri N. Vyas N. A versatile LC method for the simultaneous quantification of latanoprost, timolol and benzalkonium chloride and related substances in the presence of their degradation products in ophthalmic solution. Anal. Methods 2010 2 11 1737 1744 10.1039/c0ay00405g
    [Google Scholar]
  100. Santos M. Li M. Rustum A.M. A single RP-LC method for the determination of benzalkonium chloride and its potential impurities in benzalkonium chloride raw material. Chromatographia 2010 71 5-6 499 503 10.1365/s10337‑009‑1458‑4
    [Google Scholar]
  101. Labranche L.P. Dumont S.N. Levesque S. Carrier A. Rapid determination of total benzalkonium chloride content in ophthalmic formulation. J. Pharm. Biomed. Anal. 2007 43 3 989 993 10.1016/j.jpba.2006.09.022 17045769
    [Google Scholar]
  102. Gomez-Gomar A. Gonzalez-Aubert M.M. Garces-Torrents J. Costa-Segarra J. Determination of benzalkonium chloride in aqueous ophthalmic preparations by high-performance liquid chromatography. J. Pharm. Biomed. Anal. 1990 8 8-12 871 876 10.1016/0731‑7085(90)80135‑C 2100635
    [Google Scholar]
  103. Prieto-Blanco M.C. López-Mahía P. Prada-Rodríguez D. Analysis of residual products in benzalkonium chloride by high-performance liquid chromatography. J. Chromatogr. Sci. 1999 37 8 295 299 10.1093/chromsci/37.8.295
    [Google Scholar]
  104. Parhizkari G. Delker G. Miller R.B. Chen C. A stability-indicating HPLC method for the determination of benzalkonium chloride in 0.5% tramadol ophthalmic solution. Chromatographia 1995 40 3-4 155 158 10.1007/BF02272164
    [Google Scholar]
  105. Nikalje A.P. Gadikar R. A simple liquid chromatographic method for simultaneous determination of aceclofenac, methyl salicylate, and benzyl alcohol in pharmaceuticals. J. Pharm. Res. 2018 12 3 283 287
    [Google Scholar]
  106. Mahgoub S. Validated RP-HPLC method for quantitative determination of tolfenamic acid and benzyl alcohol in a veterinary pharmaceutical preparation. Austin Chromatogr 2017 4 1046 1050
    [Google Scholar]
  107. Mohammed Khan K. Khan A.R. Perveen S. Ullah Z. Ambreen N. Voelter W. High-performance liquid chromatographic quantitative determination of amcinonide and benzyl alcohol in pharmaceutical preparations. Open Anal. Chem. J. 2008 2 1
    [Google Scholar]
  108. Čudina O.A. Čomor M.I. Janković I.A. Simultaneous determination of bifonazole and benzyl alcohol in pharmaceutical formulations by reverse-phase HPLC. Chromatographia 2005 61 415 418 10.1365/s10337‑005‑0524‑9
    [Google Scholar]
  109. Pérez-Lozano P. García-Montoya E. Orriols A. Miñarro M. Ticó J.R. Suñé-Negre J.M. A new validated method for the simultaneous determination of benzocaine, propylparaben and benzyl alcohol in a bioadhesive gel by HPLC. J. Pharm. Biomed. Anal. 2005 39 5 920 927 10.1016/j.jpba.2005.05.033 16039086
    [Google Scholar]
  110. Whatley H. Basic principles and modes of capillary electrophoresis. In: Clin Forensic Appl Capillary Electrophor. Totowa, NJ Humana Press 2001 21 58
    [Google Scholar]
  111. Labat L. Kummer E. Dallet P. Dubost J.P. Comparison of high-performance liquid chromatography and capillary zone electrophoresis for the determination of parabens in a cosmetic product. J. Pharm. Biomed. Anal. 2000 23 4 763 769 10.1016/S0731‑7085(00)00358‑7 10975252
    [Google Scholar]
  112. Stubberud K. Studies of micellar electrokinetic chromatography as an analytical technique in pharmaceutical analysis—an industrial perspective. Doctoral dissertation, Acta Universitatis Upsaliensis
    [Google Scholar]
  113. Sako A.V.F. Dolzan M.D. Micke G.A. Fast and sensitive method to determine parabens by capillary electrophoresis using automatic reverse electrode polarity stacking mode: Application to hair samples. Anal. Bioanal. Chem. 2015 407 24 7333 7339 10.1007/s00216‑015‑8895‑8 26168974
    [Google Scholar]
  114. Uysal U.D. Güray T. Determination of parabens in pharmaceutical and cosmetic products by capillary electrophoresis. J. Anal. Chem. 2008 63 10 982 986 10.1134/S1061934808100109
    [Google Scholar]
  115. Hamoudová R. Pospíšilová M. Kavalírová A. Solich P. Šícha J. Separation and determination of clotrimazole, methylparaben and propylparaben in pharmaceutical preparation by micellar electrokinetic chromatography. J. Pharm. Biomed. Anal. 2006 40 1 215 219 10.1016/j.jpba.2005.07.001 16095858
    [Google Scholar]
  116. De Croo F. de Schutter J. Van den Bossche W. De Moerloose P. Gas chromatographic determination of parabens in various pharmaceutical dosage forms. Chromatographia 1984 18 5 260 264 10.1007/BF02270561
    [Google Scholar]
  117. Ng L.K. Hupé M. Harris A.G. Direct gas chromatographic method for determining the homologue composition of benzalkonium chlorides. J. Chromatogr. A 1986 351 554 559 10.1016/S0021‑9673(01)83537‑8
    [Google Scholar]
  118. Urakami K. Kobayashi C. Miyazaki Y. Nishijima K. Yoshimura Y. Hashimoto K. Degradation products generated by sonication of benzyl alcohol, a sample preparation solvent for the determination of residual solvents in pharmaceutical bulks, on capillary gas chromatography. Chem Pharm 2000 48 9 1299 1303 10.1248/cpb.48.1299 10993228
    [Google Scholar]
  119. Schieffer G.W. Palermo P.J. Pollard-Walker S. Simultaneous determination of methyl, ethyl, propyl, and butyl 4-hydroxybenzoates and 4-hydroxybenzoic acid in liquid antacid formulations by gas chromatography. J. Pharm. Sci. 1984 73 1 128 131 10.1002/jps.2600730136 6694070
    [Google Scholar]
  120. Cybulski Z.R. Determination of benzalkonium chloride by gas chromatography. J. Pharm. Sci. 1984 73 12 1700 1702 10.1002/jps.2600731209 6527238
    [Google Scholar]
  121. Chawla G. Ranjan C. Principle, instrumentation, and applications of UPLC: A novel technique of liquid chromatography. Open Chem. J. 2016 3 1 1 16 10.2174/1874842201603010001
    [Google Scholar]
  122. Hudalla C.J. Fountain K.J. UPLC analysis of benzalkonium chloride (BAC) in consumer products using ACQUITY UPLC CSH C18. 2019 Available from: https://www.waters.com/nextgen/us/en/library/application-notes/2013/analysis-benzalkonium-chloride-consumer-products.html?srsltid=AfmBOor2HHgEgVP0lpJP8Lhj7E1FUJNE7v0jROLmZuQidRJAxzCnZfT4
    [Google Scholar]
/content/journals/cdrr/10.2174/0125899775390873250721162514
Loading
Advancements in Analytical Techniques for Preservative Identification in Pharmaceuticals
Bentham Science Publishers ; https://doi.org/10.2174/0125899775390873250721162514
/content/journals/cdrr/10.2174/0125899775390873250721162514
/content/journals/cdrr/10.2174/0125899775390873250721162514
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: regulatory compliance ; detection limits ; GC-MS ; UV-Vis ; HPLC ; Preservatives ; analytical techniques

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test