Chiral supercritical fluid chromatography/tandem mass spectrometry for the simultaneous determination of pindolol and propranolol in metabolic stability samples.

A chiral packed-column supercritical fluid chromatographic (pSFC) system coupled to tandem mass spectrometer (MS/MS) for the rapid measurements of (R,S)-propranolol and (+/-)-pindolol in metabolic stability samples was developed. The effects of the eluent flow rates and compositions, as well as of the nebulizer temperature, on the chromatographic performance and the ionization efficiency of the analytes in positive ion mode under pSFC conditions were studied. The ionization mechanism of the analytes in the CO2/methanol atmospheric pressure chemical ionization (APCI) environments with or without the use of an additive was studied. The chiral pSFC-APCI-MS/MS approach requiring approximately 2 min per sample was applied for the simultaneous determination of two pairs of racemic drugs in in vitro samples at low nanogram per milliliter concentrations.