Published online Sep 9, 2016. doi: 10.5497/wjp.v5.i3.59
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
To investigate physicochemical stability of sevoflurane in dimethyl sulfoxide using gas chromatography with a flame ionization detector and nuclear magnetic resonance (NMR).
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.
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).
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.