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

The chiral synthesis of β-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 developed 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 detection of 3-tert.-butylamino-1,2-propanediol was first optimized with a pneumatically-assisted electrospray interface (ionspray). The APCI interface was then selected for LC–MS–MS because of the incompatibility of electrospray with n-hexane. The method was validated for both enantiomers in the 25–500 ng/ml concentration range.