Warmed diluent speeds dantrolene reconstitution.

Purpose: To define more completely the aqueous solubility of dantrolene in order to devise faster reconstitution techniques for use during malignant hyperthermia episodes.

Methods: To determine Beer's law compliance and the extinction coefficient, we measured the spectrophotometric absorbance at 385 nm of known dantrolene solutions. We added small aliquots of sterile water USP (pH 5.3; 15-40 degrees C) or buffered water (20 degrees C; pH 6.8-9.1) to dantrolene, mechanically agitated and filtered the solutions, and spectrophotometrically determined concentration. To simulate clinical reconstitution conditions, we added sterile water, 60 mL, at temperatures between 15 and 40 degrees C to dantrolene vials and measured the manual shaking time needed to create a) a suspension of small particles, and b) a clear solution.

Results: A plot of UV-vis absorbance at 385 nm vs dantrolene concentration was linear and went through the origin; the extinction coefficient is 16.1 mM(-1). At 20 degrees C, dantrolene is nearly insoluble below pH 8.8. Dantrolene is 2.8 times more soluble in 0.1 M THAM (tris-(hydroxymethyl)aminomethane) than in sterile water at pH 9.1. Dantrolene is 6.7 times more soluble in 40 degrees C than in 20 degrees C water at pH 9.5 (the pH of reconstituted dantrolene). Under clinical conditions, water temperature altered the time to create a clear solution but not a suspension (60 sec).

Conclusion: Diluting dantrolene with 40 degrees C water rather than operating-room temperature water (20 degrees C or below) would speed dantrolene reconstitution.