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Warmed diluent speeds dantrolene reconstitution

[Le diluant réchauffé accélère la reconstitution du dantrolène]

Laura W. Mitchell, PhD^* and Barbara L. Leighton, MD

¹ From the Department of Chemistry, *St. Joseph’s University, Philadelphia, Pennsylvania and
the Department of Anesthesiology, MCP Hahnemann University, Philadelphia, Pennsylvania, USA.

Address correspondence to: Dr. Barbara L. Leighton, Department of Anesthesiology, 660 S. Euclid Ave, Campus Box 8054, St Louis, Missouri 63110, USA. Phone: 314-362-2356; Fax: 314-362-1185; E-mail: bleigh{at}alumni.princeton.edu

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°C) or buffered water (20°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°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°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°C than in 20°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°C water rather than operating-room temperature water (20°C or below) would speed dantrolene reconstitution.

This article has been cited by other articles:

				D. Chartrand Intervention rapide lors d'une crise d'hyperthermie maligne/Rapid intervention for an episode of malignant hyperthermia Can J Anesth, February 1, 2003; 50(2): 104 - 107. [Full Text] [PDF]