Interference by butyl rubber stoppers in GLC analysis for theophylline.

During a study of the pharmacokinetics of theophylline using GLC analysis, unexpectedly high values occurred in a random manner. The cause of there abnormal values was investigated, and significant interference was observed when blood samples were drawn using evacuated glass tubes sealed with butyl rubber stoppers. In vitro tests using distilled water showed no apparent theophylline levels due to the additives in three commonly used tubes. However, when water was allowed to remain in contact with the butyl rubber stoppers for 1 min, an apparent theophylline content of as high as 5.5 mug/ml was observed. A contact time of 60 min resulted in apparent theophylline levels of as high as 52.3 mug/ml. It was concluded that a substance leached from the butyl rubber stoppers accounted for the spurious results.