Thomas J. Toolan, R. Wagner
Mar 1, 1959
Citations
0
Influential Citations
51
Citations
Journal
Annals of the New York Academy of Sciences
Abstract
Chlorpropamide [l-(~-chlorobenzenesulfonyl)-3-propylurea; Diabinese*] belongs to the class of arylsulfonylurea compounds, which have found widespread use in the oral treatment of diabetes mellitus. I t was felt worthwhile to study some of the physical properties of this compound and to develop a method suitable for its determination in human serum. Chlorpropamide can be characterized by a number of physical properties. The present paper deals with preliminary observations on the following: (1) titration behavior, (2) melting point, (3) ultraviolet absorption spectrum, (4) infrared absorption spectrum, (5) solubility, (6) paper chromatography, and (7) countercurrent distribution. Such data proved useful in the development of an assay method for this product. Several assay methods have been reported for 2 other arylsulfonylurea compounds: namely, tolbutamide and carbutamide.'? Forist et aZ.,2 Spingler and K a i ~ e r , ~ and Bladh and Nordtn4 developed methods for the determination of tolbutamide (l-butyl-3-~-tolylsulfonylurea) ; these were based essentially on the intense ultraviolet absorption of this compound a t 228 mp. In addition, McDonald and Sawinskis and Spingler6 described colorimetric procedures for the determination of tolbutamide. Carbutamide (l-butyl-3sulfanilylurea) can be determined in serum by diazotization and coupling reactions.' The method to be described for chlorpropamide is based on the ultraviolet absorption of this compound a t 232.5 mp in 0.01 N hydrochloric acid. It is isolated from serum by a two-stage extraction procedure which includes: (1) extraction of serum, acidified with phosphoric acid, with chloroform, and (2) re-extraction of the chloroform phase with a dilute solution of sodium carbonate. The aqueous phase from the second extraction is adjusted to p H 2 with hydrochloric acid; the chlorpropamide content is determined by measurement of the absorbance a t 232.5 mp.