Quantification of nitrendipine by stable isotope dilution and electron-capture negative ion chemical ionization.
The electron-capture properties of nitrendipine, a 1,4-dihydro-pyridine derivative with antihypertensive activity, have been applied to develop a sensitive and specific assay in biological fluids using capillary column gas chromatography and measurement in negative ion chemical ionization mode. The synthesis of a 13C4-labelled analogue suitable as a biological internal standard for bioavailability studies and of a 2H8-labelled analogue, which serves as internal standard, is described. The electron-capture positive ion chemical ionization and electron-capture negative ion chemical ionization mass spectra of nitrendipine and its isotope-labelled analogues are compared. The assay has a detection limit of 100 pg ml-1 plasma with a coefficient of variation of 10.2% using the selected ion monitoring mode and electron-capture negative ion chemical ionization. The method is specific, sensitive and accurate to determine terminal half-life times after intravenous and oral administration of nitrendipine and its 13C-analogue. From the nearly identical plasma concentration-time profile of nitrendipine and its 13C-labelled analogue, an isotopic effect can be excluded. Thus, the synthesized 13C4-analogue should be well suited as a biological standard for bioavailability studies.
D000328:Adult; D002247:Carbon Isotopes; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D009568:Nitrendipine / Q000097:blood*
D002247:Carbon Isotopes; D009568:Nitrendipine; D003903:Deuterium