Determination of a new calcium antagonist and its main metabolite in plasma by thermospray liquid chromatography-mass spectrometry.

A highly sensitive thermospray liquid chromatographic-mass spectrometric method has been developed for the simultaneous determination of FRC-8653 (I), a new calcium antagonist, and its main metabolite (M-4) in plasma. A deuterated analogue of I was added to the plasma as the internal standard. After the purification and concentration of the plasma sample on bonded-phase disposable columns, the extract was injected into the thermospray liquid chromatograph and analysed by selected-ion monitoring mass spectrometry. The calibration curves obtained were linear over the concentration range 0.5-100 ng/ml. The limits of quantification are 0.5 ng/ml for I and 1 ng/ml for M-4 in plasma, which are sufficient to evaluate plasma concentrations after oral administration to rats.