Vaporization Enthalpy and Vapor Pressure of Valproic Acid by Correlation Gas Chromatography

The vaporization enthalpy of valproic acid (2-propylpentanoic acid) is reported, and the vapor pressures of a series on aliphatic carboxylic acids are used to evaluate its vapor pressure as a function of temperature. The vaporization enthalpy was derived by correlation-gas chromatography. This resulted in a vaporization enthalpy, ΔHvap(298.15 K) of (74.8 ± 2.4) kJ·mol−1. Vapor pressures from T/K = 298.15 to boiling temperature of valproic acid are also reported. A normal boiling temperature of T/K = 492.8 (lit., 494−5 K) and a vapor pressure of (2.2 ± 0.3) Pa has been evaluated for valproic acid at T/K = 298.15. This compares favorably with an Environmental Protection Agency estimate of 6.1 Pa. ■ INTRODUCTION Valproic acid, 2-propylpentanoic acid, Figure 1, and its sodium salt, also marketed under various trade names including, Valparin, Depakote, Depakote ER, Depacon, and Stavzor, has been used clinically in the treatment of bipolar disorder, epilepsy, other mood disorders, and for neuropatic pain and fibromyalgia. It has also been of recent interest in HIV treatment although further studies found no long-term benefits from its use. Valproic acid may also have implications in the treatment of various cancers. Despite the fact that valproic acid has been in use in various therapies for over 30 years, there is very little information available regarding its thermochemical properties in the literature. The Environmental Protection Agency (EPA), for example, cites a vapor pressure of 6.1 Pa at T/K = 298, and this is an estimated value. Similarly, for its vaporization enthalpy, an estimated value of (50.3 ± 6.0) kJ·mol−1 is predicted by ACD Laboratories software as cited by SciFinder Scholar. Another simple equation for the estimation of vaporization enthalpies of singly substituted alkanes such as valproic acid is given by eq 1: