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Selected ion monitoring analysis of NB‐818, a new calcium entry blocker in a series of dihydropyridines, in human plasma
Author(s) -
Takano Terukazu,
Hata Shunsuke
Publication year - 1988
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.1200170611
Subject(s) - chemistry , silylation , moiety , chromatography , detection limit , calibration curve , hydroxymethyl , mass spectrometry , pharmacokinetics , selected ion monitoring , gas chromatography–mass spectrometry , stereochemistry , organic chemistry , catalysis , pharmacology , medicine
NB‐818 is expected in clinical use to produce an antihypertensive effect and simultaneously to promote an increase in cerebral blood flow, owing to its vasodilator activity. To determine NB‐818 levels in human plasma for pharmacokinetic studies, a capillary column gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) method was employed. Because NB‐818 was degraded under GC conditions, stable derivatives had to be prepared for GC/MS measurements. Reaction of NB‐818 with silylation agents produced derivatives quantitatively. In the silylation, however, the carbomoyl group of NB‐818 was replaced by silyl moieties. NB‐818 is possibly metabolized at the carbamate moiety alone, giving a compound with a hydroxymethyl group in place of the carbamoyloxymethyl group. Since this compound and NB‐818 gave the same derivative, efforts were devoted to separating them. A detection limit below 0.1 ng ml −1 was attained. The calibration curve was linear in the concentration range 0.1–10 ng ml −1 ( r = 0.9998), and the coefficient of variation was 5.5% and 3.1% at concentrations of 1 and 10 ng ml −1 , respectively.