Determination of the enantiomers of 3-tert.-butylamino-1,2-propanediol by high-performance liquid chromatography using mass spectrometric detection

The chiral synthesis of beta beta -blockers such as (S)-timolol requires a sensitive analytical method for the enantioseparation of its intermediate, 3-tert.-butylamino-1,2-propanediol, in the ng/ml range. The method develope d is based on on-line normal-phase LC-MS-MS using a chiral stationary phase and an atmospheric pressure chemical ionization (APCI) interface. The MS d etection of 3-tert.-butylamino-1,2-propanediol was first optimized with a p neumatieally-assisted electrospray interface (ionspray). The APCI interface was then selected for LC-MS-MS because of the incompatibility of electrosp ray with n-hexane. The method was validated for both enantiomers in the 25- 500 ng/ml concentration range. (C) 2000 Elsevier Science B.V. All rights re served.