Specific determination of plasma nicardipine hydrochloride levels by gas chromatography-mass spectrometry.
A highly specific method for the determination of the plasma level of the potent vasodilator 2-(N-benzyl-N-methylamino)ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine carboxylate hydrochloride (nicardipine hydrochloride) in rats, dogs and humans is described. N-d3-Methyl derivative was added as an internal standard, then the plasma was extracted with diethyl ether and subjected to thin-layer chromatography (TLC) to remove the pyridine analogue, one of the drug's metabolites. The area corresponding to the unchanged drug was identified with simultaneously run N-d7-benzyl derivative under UV light. The unchanged drug with a 1,4-dihydropyridine structure was oxidized with nitrous acid to its pyridine anlogue, which was stable for gas chromatography, and subjected to mass spectrometry at m/e 134 (nicardipine) and m/e 137 (N-d3-methyl derivative). The sensitivity limit was 5 g ml-1. The ratio of the unchanged drug to the value obtained by the method without TLC separation was 100% for rats and 80% for dogs and humans at almost all times investigated after dosing. These results demonstrate that in these species, the amount of pyridine analogue in plasma was very small compared with that of the parent drug.
D000818:Animals; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood*; D051381:Rats; D012016:Reference Values; D013997:Time Factors
D011725:Pyridines; D009529:Nicardipine; D009543:Nifedipine