The chemical and physical stability of a 1:1 mixture of propofol and methohexital.

Anesthetic drugs are frequently mixed or coadministered to optimize anesthetic effects while minimizing adverse effects. Methohexital advantages include its low cost and rapid onset, while propofol provides improved airway anesthesia and extremely rapid clearance from the plasma. Therefore, a mixture of these agents might well be superior to either drug given alone. We wished to determine whether a mixture of methohexital and propofol is chemically and physically stable. A 1:1 mixture of propofol 10 mg/ml and methohexital was prepared. At times varying from 0 to 48 hours, mixtures with an internal standard of thymol kept at room temperature were thrice extracted with a 2:1 v/v mixture of diethyl ether:pentane, dried under nitrogen, and treated overnight with bis-trimethylsilyl-trifluoroacetamide. The resultant derivatives were transferred to microsample vials and analyzed by GC-MS. Drug stability was quantified by electronic integration of peak areas representing characteristic ions for each drug. For each sample, the peak area of the methohexital ion (m/z 239) or propofol ion (m/z 235) relative to the corresponding thymol ion (m/z 207) served as an index of the concentration of the drug in the sample. At times varying from 0 to 48 hours, mixtures without thymol were used to determine mean droplet size of the particles. This was accomplished using both an Accusizer and a Nicomp 370 Particle Sizer. One way ANOVA tested for significant changes in drug concentrations and mean particle size as a function of time. There was no significant breakdown of propofol or methohexital when combined in a 1:1 mixture and allowed to stand for 48 hours, nor was there an increase in particle size suggestive of emulsion instability. We concluded that a 1:1 mixture of propofol and methohexital was stable up to 48 hours after mixing.