Determination of SA-466 in human whole blood and urine by electron capture-gas liquid chromatography.

Abstract

A highly sensitive and specific gas chromatographic method for the determination of SA-446 [(2R, 4R)-2-(2-hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinecarboxylic acid] [an angiotensin converting enzyme inhibitor and potential antihypertensive agent] in human whole blood and urine was established. The mercapto group of SA-446 was alkylated completely with pentafluorobenzyl bromide (PFBB) and then the remaining hydroxyl and carboxyl groups were methylated with diazomethane. As little as 10 pg of the derivatized SA-446 is detectable by the electron capture technique. The mean recoveries of SA-446 from whole blood and urine by the present method were 95.5 and 93.5%, respectively. The calibration curves for SA-446 were linear in the concentration ranges of 10-10000 ng/ml of whole blood and 0.1-100 .mu.g/ml of urine. The SD with this method was < 3.0%. This method is highly sensitive, and a small sample size of 250 .mu.l is enough to determine SA-446 in human whole blood and urine.