CAPILLARY GAS-CHROMATOGRAPHIC DETERMINATION WITH ELECTRON-CAPTURE DETECTOR OF BETA-PROPIOLACTONE IN BIOLOGICAL-MATERIALS

A method has been developed for the determination of beta-propiolactone by derivatizing it to the volatile N-hexyl-3-heptafluorobutanoyloxypropanamide, which can be separated and identified by a capillary CP-SII 8 column, and detected by an electron capture detector (ECD). First, beta-propiolactone is reacted with N-hexylamine to yield N-hexyl-3-hydroxypropanamide. The fluorobutanoyl ester derivative is next prepared by using heptafluorobutyric acid anhydride in the presence of trimethylamine. The method is very sensitive, simple, and specific, and can be used to detect and quantitate residual beta-propiolactone in lyophilized biological materials. The limit of detection is 0.2 ppm beta-propiolactone in a 50 mg sample; however, because of variability at low levels, the limit of quantitation is 1 ppm. Detector response was linear for 2-500 ng beta-propiolactone. Recoveries were 98% or greater from lyophilized vaccines spiked at the 2-20 ppm level. No side products or interference peaks were observed in the derivatization reaction.