Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis
Javier Fidalgo,* Pierre-Antoine Deglesne,* Rodrigo Arroyo,* Lilian Sepúlveda,* Evgeniya Ranneva, Philippe Deprez Scientific Department, Skin Tech Pharma Group, Castello D’Empúries, Cataluña, Spain *These authors contributed equally to this work Background:...
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Dove Medical Press
2018
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oai:doaj.org-article:19891d7159cf4541b323cf3323a0f5702021-12-02T06:02:25ZDetection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis1179-1470https://doaj.org/article/19891d7159cf4541b323cf3323a0f5702018-10-01T00:00:00Zhttps://www.dovepress.com/detection-of-a-new-reaction-by-product-in-bdde-cross-linked-autoclaved-peer-reviewed-article-MDERhttps://doaj.org/toc/1179-1470Javier Fidalgo,* Pierre-Antoine Deglesne,* Rodrigo Arroyo,* Lilian Sepúlveda,* Evgeniya Ranneva, Philippe Deprez Scientific Department, Skin Tech Pharma Group, Castello D’Empúries, Cataluña, Spain *These authors contributed equally to this work Background: Hyaluronic acid (HA), a naturally occurring polysaccharide, is used in the production of dermal fillers for esthetic purposes. As it has a few days of half-life in human tissues, HA-based dermal filler is chemically modified to increase its lifetime in the body. The most common modification used in commercial HA-based filler is the cross-linking of HA chains using 1,4-butanediol diglycidyl ether (BDDE) as cross-linking agent. Residual, or unreacted, BDDE is considered nontoxic when it is <2 parts per million (ppm); therefore, the quantification of residual BDDE in the final dermal filler is mandatory to ensure the safety of the patients. Materials and methods: The present study describes the detection and characterization of one by-product of the cross-linking reaction between BDDE and HA in alkaline conditions by combining both liquid chromatography and mass spectroscopy (LC–MS). Results: After different analyses, it was found that the alkaline conditions and the high temperatures employed to sterilize the HA–BDDE hydrogel promote the formation of this new by-product, a “propene glicol-like” compound. LC–MS analysis confirmed that this by-product have the same monoisotopic mass as that of BDDE, a different retention time (tR), and also a different UV absorbance (λ=200 nm) pattern. Unlike BDDE, it was observed in the LC–MS analysis that this by-product had a higher detection at 200 nm in the same assay conditions. Conclusion: These results suggest that this new compound does not have an epoxide on its structure. The discussion is open to assess the risk of this new by-product found in the production of HA–BDDE hydrogels (HA dermal fillers) for commercial purposes. Keywords: hyaluronic acid, HA dermal fillers, cross-linked hyaluronic acid, BDDE, LC–MS analysis, BDDE by-product.Fidalgo JDeglesne PAArroyo RSepúlveda LRanneva EDeprez PDove Medical PressarticleHyaluronic acidHA dermal fillersCross-linked hyaluronic acidBDDELC-MS analysisBDDE byproduct.Medical technologyR855-855.5ENMedical Devices: Evidence and Research, Vol Volume 11, Pp 367-376 (2018) |
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Hyaluronic acid HA dermal fillers Cross-linked hyaluronic acid BDDE LC-MS analysis BDDE byproduct. Medical technology R855-855.5 |
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Hyaluronic acid HA dermal fillers Cross-linked hyaluronic acid BDDE LC-MS analysis BDDE byproduct. Medical technology R855-855.5 Fidalgo J Deglesne PA Arroyo R Sepúlveda L Ranneva E Deprez P Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis |
| description |
Javier Fidalgo,* Pierre-Antoine Deglesne,* Rodrigo Arroyo,* Lilian Sepúlveda,* Evgeniya Ranneva, Philippe Deprez Scientific Department, Skin Tech Pharma Group, Castello D’Empúries, Cataluña, Spain *These authors contributed equally to this work Background: Hyaluronic acid (HA), a naturally occurring polysaccharide, is used in the production of dermal fillers for esthetic purposes. As it has a few days of half-life in human tissues, HA-based dermal filler is chemically modified to increase its lifetime in the body. The most common modification used in commercial HA-based filler is the cross-linking of HA chains using 1,4-butanediol diglycidyl ether (BDDE) as cross-linking agent. Residual, or unreacted, BDDE is considered nontoxic when it is <2 parts per million (ppm); therefore, the quantification of residual BDDE in the final dermal filler is mandatory to ensure the safety of the patients. Materials and methods: The present study describes the detection and characterization of one by-product of the cross-linking reaction between BDDE and HA in alkaline conditions by combining both liquid chromatography and mass spectroscopy (LC–MS). Results: After different analyses, it was found that the alkaline conditions and the high temperatures employed to sterilize the HA–BDDE hydrogel promote the formation of this new by-product, a “propene glicol-like” compound. LC–MS analysis confirmed that this by-product have the same monoisotopic mass as that of BDDE, a different retention time (tR), and also a different UV absorbance (λ=200 nm) pattern. Unlike BDDE, it was observed in the LC–MS analysis that this by-product had a higher detection at 200 nm in the same assay conditions. Conclusion: These results suggest that this new compound does not have an epoxide on its structure. The discussion is open to assess the risk of this new by-product found in the production of HA–BDDE hydrogels (HA dermal fillers) for commercial purposes. Keywords: hyaluronic acid, HA dermal fillers, cross-linked hyaluronic acid, BDDE, LC–MS analysis, BDDE by-product. |
| format |
article |
| author |
Fidalgo J Deglesne PA Arroyo R Sepúlveda L Ranneva E Deprez P |
| author_facet |
Fidalgo J Deglesne PA Arroyo R Sepúlveda L Ranneva E Deprez P |
| author_sort |
Fidalgo J |
| title |
Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis |
| title_short |
Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis |
| title_full |
Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis |
| title_fullStr |
Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis |
| title_full_unstemmed |
Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis |
| title_sort |
detection of a new reaction by-product in bdde cross-linked autoclaved hyaluronic acid hydrogels by lc–ms analysis |
| publisher |
Dove Medical Press |
| publishDate |
2018 |
| url |
https://doaj.org/article/19891d7159cf4541b323cf3323a0f570 |
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