Determination of nilvadipine in human plasma by capillary column gas chromatography-negative-ion chemical-ionization mass spectrometry.

A highly sensitive and specific method for the determination of nilvadipine, a new dihydropyridine calcium antagonist, in human plasma is described. A deuterated analogue of nilvadipine is added to the plasma as an internal standard. The agent and its internal standard are extracted at pH 9 from the plasma into a benzene--n-hexane (1:1) mixture. The extract is analysed by fused-silica capillary column gas chromatography--negative-ion chemical-ionization mass spectrometry with methane as the reagent gas. The mass spectrometer is set to monitor the negative molecular ions of the agent and internal standard. Quantitation is possible down to 0.01 ng/ml using 1 ml of plasma. The coefficients of variation of the method are 6.4 and 2.1% at the 0.01 and 0.1 ng/ml levels, respectively. Plasma levels obtained with this method are given for four healthy volunteers who had received a 6-mg oral dose of nilvadipine.