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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacology. Sep 9, 2016; 5(3): 59-67
Published online Sep 9, 2016. doi: 10.5497/wjp.v5.i3.59
Innovate combination of sevoflurane dilution in dimethyl sulfoxide: A stability study by gas chromatography and nuclear magnetic resonance
F Dámaso Fernández-Ginés, Sergio García-Muñoz, Héctor Mateo-Carrasco, Miguel Ángel Rincón-Cervera, Manuel Cortiñas-Sáenz, José Antonio Morales-Molina, Carmen Fernández-Sánchez, Juan Miguel Expósito-López, Ignacio Rodríguez-García
F Dámaso Fernández-Ginés, Carmen Fernández-Sánchez, Department of Pharmacy, Torrecárdenas Hospital, 04009 Almería, Spain
Sergio García-Muñoz, University of Almería, 04120 Almería, Spain
Héctor Mateo-Carrasco, Aseptic Services Unit, Department of Pharmacy, Northampton General Hospital, Northampton NN1 5BD, United Kingdom
Miguel Ángel Rincón-Cervera, Institute of Nutrition and Food Technology, University of Chile, 1058 Santiago, Chile
Manuel Cortiñas-Sáenz, Department of Anesthesiology and Pain Management, Torrecárdenas Hospital, 04009 Almería, Spain
José Antonio Morales-Molina, Department of Pharmacy, Agencia Pública Empresarial Sanitaria Hospital de Poniente, El Ejido, 04700 Almería, Spain
Juan Miguel Expósito-López, Ignacio Rodríguez-García, Department of Chemistry and Physics, University of Almería, 04120 Almería, Spain
Author contributions: Fernández-Ginés FD, García-Muñoz S and Mateo-Carrasco H contributed equally to this work; Rincón-Cervera MÁ participated in the acquisition, analysis, and interpretation of chromatograms; Cortiñas-Sáenz M, Morales-Molina JA and Fernández-Sánchez C were the guarantor and designed the study; Expósito-López JM participated in the acquisition, analysis, and interpretation of nuclear magnetic resonance spectra; Rodríguez-García I revised the article critically for important intellectual content.
Institutional review board statement: This research has not involved human and/or animal subjects, hence none IRBS was required.
Informed consent statement: This research has not involved human and/or animal subjects, hence none ICS was required.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Héctor Mateo-Carrasco, MPharm, PhD, MRPharmS, Specialist Pharmacist Cancer Services, Aseptic Services Unit, Department of Pharmacy, Northampton General Hospital, Cliftonville Road, Northampton NN1 5BD, United Kingdom.
hector.mateo-carrasco@ngh.nhs.uk
Telephone: +44-1604-533354
Received: April 8, 2016
Peer-review started: April 11, 2016
First decision: July 21, 2016
Revised: July 26, 2016
Accepted: August 30, 2016
Article in press: August 31, 2016
Published online: September 9, 2016
Processing time: 47 Days and 20.7 Hours
AIM
To investigate physicochemical stability of sevoflurane in dimethyl sulfoxide using gas chromatography with a flame ionization detector and nuclear magnetic resonance (NMR).
METHODS
Undiluted sevoflurane, plus dilutions 1:2, 1:5, 1:10, 1:25, and 1:50 in dimethyl sulfoxide were prepared in a vertical laminar flow cabinet class II type B and stored at different temperatures (23 °C, 6 °C, and -10 °C) for 45 d. Sterile 1 mL polypropylene amber syringes to minimize light degradation, caps and needles were used. The presence of sevoflurane and its degradation products in the samples was determined by gas chromatography with flame ionization detector (260 °C, 40 min), and by 1H, 19F, and proton-decoupled 19F nuclear magnetic resonance.
RESULTS
The gas chromatography analysis showed sevoflurane and dimethyl sulfoxide (DMSO) retention times were 2.7 and 13.0 min, respectively. Pure DMSO injection into the column resulted in two additional peaks at 2.1 and 2.8 min. The same sevoflurane peak at 2.7 min was observed in all the dilutions at -10 °C, 4 °C and 25 °C. The NMR spectra showed signals consistent with the sevoflurane structure in all the dilutions at -10 °C, 4 °C and 25 °C. In the 1H spectrum, two signals corresponding to the sevoflurane molecule were observed at 5.12 and 4.16 parts per million (ppm). In the 19F-NMR spectrum, two signals were observed at chemical shift -76.77 ppm and chemical shift -157.13 ppm. In the 19F{1H}-NMR CPD, two signals were observed at chemical shift -76.77 ppm and chemical shift -157.13 ppm. The first one showed a doublet (JF-F = 3.1 Hz) which integrated by six fluorine nuclei from the hexafluoro-isopropyl group. The second signal was integrated by a fluorine atom and showed a septuplet (JF-F = 3.1 Hz).
CONCLUSION
This study shows that different concentrations of sevoflurane in dimethyl sulfoxide retain their chemical composition after exposure to different temperatures for a period of 45 d.
Core tip: Direct topical application of anesthetic sevoflurane has recently shown beneficial properties in the management of chronic vascular ulcers. A more convenient formulation could be obtained using solutions of sevoflurane in a miscible solvent such as dimethyl sulfoxide. However, no study has yet assessed the physicochemical and pharmaceutical stability of these formulations. Different concentrations of sevoflurane in dimethyl sulfoxide were stored over 45 d at -10 °C, 4 °C and 25 °C and assayed by gas chromatography with a flame ionization detector and nuclear magnetic resonance, showing that molecular structures remained unaltered after exposure to a range of temperatures.
