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A selected ion monitoring method for quantifying simvastatin and its acid form in human plasma, using the ferroceneboronate derivative
Author(s) -
Takano Terukazu,
Abe Shinnosuke,
Hata Shunsuke
Publication year - 1990
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.1200190910
Subject(s) - simvastatin , chromatography , chemistry , metabolite , extraction (chemistry) , detection limit , selected ion monitoring , mass spectrometry , calibration curve , gas chromatography–mass spectrometry , carboxylic acid , yield (engineering) , derivative (finance) , biochemistry , pharmacology , materials science , medicine , economics , financial economics , metallurgy
Simvastatin, a pro‐drug lactone, forms the open carboxylic acid as a major metabolite that inhibits the activity of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase. Simvastatin and the acid in plasma were quantified by a gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) method. These drugs were separated by solid‐phase extraction and independently converted into a 1,3‐diol‐type compound. This compound reacted with ferroceneboronic acid to yield the cyclic boronate that gave satisfactory mass spectra for GC/MS/SIM measurements. The spectrum was dominated by the molecular ion appearing as the base peak, thereby leading to a sensitive and selective assay. The calibration curves for simvastatin and the acid were linear in their concentration range of 0.1–10 ng ml −1 , where the values of coefficient of variation for both drugs were below 8%, except for the value of 11% for simvastatin at a concentration of 0.1 ng ml −1 . The quantification limit for both drugs was 0.1 ng ml −1 on the basis of a signal‐to‐noise ratio of 4:1.