Compound A

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Abstract
Compound A is a degradation product of sevoflurane. Knowledge of the solubility of Compound A, CH,F-O-C(==CF,)(CF,), in blood and other solvents would aid in the definition of its kinetics. Accordingly, we determined solvent/gas partition coefficients of Compound A for saline (0.166 ? 0.002 (mean -C SD; n = 41) and olive oil (20.1 -C 1.1 (n = 41). Measurement of solubility in blood was confounded by degradation of Compound A in blood and blood components. If a mix- ture of 99.3% saline and 0.7% oil provides the solubility equivalent to that possessed by blood (as it does for the parent compound, sevoflurane), then blood solubility and solubility in plasma, albumin, red blood cells, or pure hemoglobin is approximately 0.31. The order of Compound A degradation was human plasma = rat blood > whole human blood > 5% human serum albu- min = washed human red blood cells (hematocrit 50%) = 5% pure hemoglobin. Presuming a solvent/gas par- tition coefficient of 0.31, respective approximate times for 50% degradation equaled 2.7,2.8,4.6,9.9,11.0, and 12 min. The accuracy of these approximations was lim- ited by the need to estimate, rather than determine, the solubility of Compound A in such solvents. Pasteuriza- tion (heating to 60°C for 12 h) or pretreatment with N-ethylmaleimide (a compound that reversibly binds to sulfhydryl groups) decreased the degradation rate in plasma. These results suggest that degradation arises, at least in part, from reaction of Compound A with pro- teins in blood, possibly from covalent reaction of Com- pound A with protein and/or from an enzymatically mediated reaction. The products of degradation, the binding sites, and the clinical implications of such bind- ing and degradation remain to be determined. (Anesth Analg 1996;83:849-53)