Analysis of hydroxyurea in capsules and aqueous solution and stability study with capillary gas chromatography and thermionic (N-P) specific detection.

Abstract

A method for the analysis of hydroxyurea (HU) in solutions, powder, or capsules by use of capillary gas chromatography with N-P thermionic specific detection is described. Upon injection of an HU solution in a methanol and acetone mixture, the drug formed pyridine which was well separated from the internal standard (thiotepa) on a 30-m fused-silica, SE-30 capillary column with temperature programming. The peak height ratio versus concentration standard curves were linear with correlation coefficient ranging between 0.9942 and 0.9993. The coefficients of variation at 5, 25, and 50 micrograms/L were 7.2, 5.7, and 5.5%, respectively. Hydroxyurea was extracted from powder or capsule formulations with a mixture of methanol and acetone (50:50, v:v), and the percentage found of the label claim for 10 capsules ranged between 96.7 and 104.9 (mean = 100.1; CV = 2.7%). Further, this assay was used to examine the stability of hydroxyurea in aqueous solutions at 4, 23, and 45 degrees C, and the apparent first-order rate constants observed at these temperatures were 0.06407, 0.08113, and 0.1293 day-1, respectively; the activation energy was 3011 cal.K-1.mol-1.