A selected ion monitoring method for quantifying simvastatin and its acid form in human plasma, using the ferroceneboronate derivative

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.