Studies on the Instability of Chlorhexidine, Part I: Kinetics and Mechanisms

Zong, Zhixin; Kirsch, Lee E.

doi:10.1002/jps.23151

Cited by 25 publications

(11 citation statements)

References 10 publications

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“…Chlorhexidine may undergo hydrolysis in alkaline solutions, yielding mainly p-chloroaniline (pCA) or reacting with different components of the medium (Mohammed, Abdel Aziz, 2017). pCA is the main product of its degradation pathway in alkaline conditions (Zong, Kirsch, 2012). According to Lin et al (2015), light can also accelerate the by-product formation.…”

Section: Resultsmentioning

confidence: 99%

Toxicological effects of ciprofloxacin and chlorhexidine on growth and chlorophyll a synthesis of freshwater cyanobacteria

Azevedo

Vaz

Barbosa

et al. 2019

Braz. J. Pharm. Sci.

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Cyanobacteria are phytoplanktonic microorganisms that are susceptible to the deleterious effects of pharmaceutical residues in the aquatic environment, which poses a challenge to the environment exposed to diverse pharmaceutical products and their potential effects. The objective of this study was to evaluate the effects of the antibiotic substances ciprofloxacin and chlorhexidine in pharmaceutical preparations on the growth and production of chlorophyll of two cyanobacterial strains, Microcystis aeruginosa and Microcystis panniformis, isolated from a lake in a Brazilian environmental protection area. The EC 50 and EC 10 of chlorhexidine for M. aeruginosa were 206.4 μg/L and 108.5 μg/L, respectively, and for M. panniformis were 171.4 μg/L and 116.6 μg/L, respectively. The EC 50 and EC 10 of ciprofloxacin for M. aeruginosa were 17.24 μg/L and 3.21 μg/L, respectively, and for M. panniformis were 13.56 μg/L and 1.50 μg/L, respectively. The toxicity of the antibiotic ciprofloxacin (drug) and chlorhexidine (standard solution) to the Microcystis species was demonstrated, and these species were both very sensitive to ciprofloxacin. Our results suggest that the strains of M. aeruginosa and M. panniformis may be affected by exposure to residues of ciprofloxacin (>1.5 μg/L), which may represent a risk to the survival of aquatic species.

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Section: Resultsmentioning

confidence: 99%

Toxicological effects of ciprofloxacin and chlorhexidine on growth and chlorophyll a synthesis of freshwater cyanobacteria

Azevedo

Vaz

Barbosa

et al. 2019

Braz. J. Pharm. Sci.

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“…Since diluted or opened CHX and BZK may have decreased bactericidal/bacteriostatic potency over a period of time, it is important to adhere to an expiration date. Based on its chemical structure and the presence of an amide functional group, the degradation of CHX is expected under different stress conditions, including autoclaving [41], use in antacid suspensions [42], pH [43], and photocatalytic degradation [44]. On the other hand, BZK is a mixture of alkylbenzyldimethylammonium chlorides that usually contain C-10, C-12, C-14, and C-16 homologs [45].…”

Section: Discussionmentioning

confidence: 99%

Effects of Extended Storage of Chlorhexidine Gluconate and Benzalkonium Chloride Solutions on the Viability of Burkholderia cenocepacia

Ahn¹,

Kim²,

Lee³

et al. 2017

Journal of Microbiology and Biotechnology

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Chlorhexidine gluconate (CHX) and benzalkonium chloride (BZK) formulations are frequently used as antiseptics in healthcare and consumer products. Burkholderia cepacia complex (BCC) contamination of pharmaceutical products could be due to the use of contaminated water in the manufacturing process, over-diluted antiseptic solutions in the product, and the use of outdated products, which in turn reduces the antimicrobial activity of CHX and BZK. To establish a "safe use" period following opening containers of CHX and BZK, we measured the antimicrobial effects of CHX (2-10 μg/ml) and BZK (10-50 μg/ml) at sublethal concentrations on six strains of using chemical and microbiological assays. CHX (2, 4, and 10 μg/ml) and BZK (10, 20, and 50 μg/ml) stored for 42 days at 23°C showed almost the same concentration and toxicity compared with freshly prepared CHX and BZK on strains. When 5 μg/ml CHX and 20 μg/ml BZK were spiked to six strains with different inoculum sizes (10⁰ -10⁵ CFU/ml), their toxic effects were not changed for 28 days. strains in diluted CHX and BZK were detectable at concentrations up to 10² CFU/ml after incubation for 28 days at 23°C. Although abiotic and biotic changes in the toxicity of both antiseptics were not observed, our results indicate that strains could remain viable in CHX and BZK for 28 days, which in turn, indicates the importance of control measures to monitor BCC contamination in pharmaceutical products.

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“…Neither Krishnamurthy and Sudhakaran[ 28 ] nor Basrani BR et al [ 9 ] discussed para-chloro amide moiety of CHX or CHX derivative. Zong and Kirsch[ 30 ] tested the pH-dependant chlorhexidine instability and concluded that chlorhexidine degradation into PCA is more in an acidic medium as compared to the alkali medium, which could be the cutoff proof that NaOCl is not responsible for PCA formation due to its alkali nature.…”

Section: Discussionmentioning

confidence: 99%

Decoding the perplexing mystery of para-chloroaniline formation: A systematic review

Khatib

Ameer²,

Mannur³

et al. 2020

J Int Soc Prevent Communit Dent

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A BSTRACT Objective: The objective of this article was to understand and decode the mystery of the formation of para-chloroaniline (PCA). The ingredient of the brown precipitate after mixing sodium hypochlorite (NaOCl) and chlorhexidine gluconate (CHX) is still in debate. Materials and Methods: Various studies adopt a different methodology to substantiate that it may contain PCA, which is a carcinogenic agent. The purpose of this systematic review is to evaluate the relationship between PCA and brown precipitate. Two reviewers independently conducted a comprehensive literature search. The MEDLINE, Embase, Cochrane, and PubMed databases were searched. In addition, the bibliographies were manually searched. There was no disagreement between the two reviewers. This review was reported and conducted in step with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Of 233 articles, only 13 articles met the inclusion criteria. Available scientific evidence was more supportive that the brown precipitate form after mixing NaOCl and CHX may form para-chloroamide moiety rather than free PCA, and PCA may be the by-product of CHX degradation. Conclusion: On the basis of the current evidence and data extracted from the various databases, it can be concluded that the mixture of sodium hypochlorite and chlorhexidine does not form PCA, and PCA may be the by-product of high concentrated chlorhexidine. Further studies are required to substantiate the evidence.

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Studies on the Instability of Chlorhexidine, Part I: Kinetics and Mechanisms

Cited by 25 publications

References 10 publications

Toxicological effects of ciprofloxacin and chlorhexidine on growth and chlorophyll a synthesis of freshwater cyanobacteria

Toxicological effects of ciprofloxacin and chlorhexidine on growth and chlorophyll a synthesis of freshwater cyanobacteria

Effects of Extended Storage of Chlorhexidine Gluconate and Benzalkonium Chloride Solutions on the Viability of Burkholderia cenocepacia

Decoding the perplexing mystery of para-chloroaniline formation: A systematic review

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