Study of the physicochemical properties of aqueous dantrolene solutions by differential pulse polarography

Dantrolene is a skeletal-muscle relaxant which exists in three different forms over the pH range 0-14, corresponding to the cation H(2)A(+), neutral species HA and anion A(-). Dantrolene is slightly soluble in water and is polarographically reducible over the whole pH range. The acid dissociation constants of the ionic species were investigated by means of differential pulse polarography (H(2)A(+)/HA equilibrium with pK(a1) = 2.02 +/- 0.05) and potentiometry (HA/pK(a2) = 7.49 +/- 0.05). It was shown that differential pulse polarography is a valid alternative method when the pK(a) values of an electroactive drug cannot be determined by potentiometric or spectrophotometric methods. Polarography was also used to monitor the stability of the drug in acidic media and its extraction by chloroform.