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 serum 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.
Takano
T
T
Drug Metabolism, Banyu Pharmaceutical Co. Ltd. Tokyo, Japan.
Abe
S
S
Hata
S
S
D005296:Ferrous Compounds; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000097:blood; D000075163:Metallocenes; D008745:Methylation; D009942:Organometallic Compounds; D019821:Simvastatin
D005296:Ferrous Compounds; D000075163:Metallocenes; D009942:Organometallic Compounds; D008148:Lovastatin; D019821:Simvastatin; C004998:ferrocene