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Quantification of nitrendipine by stable isotope dilution and electron‐capture negative ion chemical ionization
Author(s) -
Fischer C.,
Heuer B.,
Heuck K.,
Eichelbaum M.
Publication year - 1986
Publication title -
biomedical and environmental mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0887-6134
DOI - 10.1002/bms.1200131202
Subject(s) - chemical ionization , chemistry , nitrendipine , ionization , analytical chemistry (journal) , ion , selected ion monitoring , isotope dilution , electron ionization , chromatography , mass spectrometry , ion source , gas chromatography–mass spectrometry , organic chemistry , calcium
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 13 C 4 ‐labelled analogue suitable as a biological internal standard for bioavailability studies and of a 2 H 8 ‐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 13 C‐analogue. From the nearly identical plasma concentration‐time profile of nitrendipine and its 13 C‐labelled analogue, an isotopic effect can be excluded. Thus, the synthesized 13 C 4 ‐analogue should be well suited as a biological standard for bioavailability studies.