Quantitation of cerivastatin and its seven acid and lactone biotransformation products in human serum by liquid chromatography-electrospray tandem mass spectrometry

J Chromatogr B Biomed Sci Appl. 1999 Dec 24;736(1-2):19-41. doi: 10.1016/s0378-4347(99)00390-4.

Abstract

A method for the simultaneous quantitation of cerivastatin (acid) and its biotransformation products, cerivastatin lactone, M-1 (acid), M-1 lactone, M-23 (acid), M-23 lactone, M-24 (acid) and M-24 lactone, in human serum by high-performance liquid chromatography (LC) with positive ion electrospray tandem mass spectrometry (MS-MS) was developed and validated. The method involves extraction of cerivastatin and its biotransformation products from acidified human serum (0.5 ml) using methyl tert.-butyl ether. The standard curve ranges in human serum were from 0.0100 to 10.0 ng/ml for cerivastatin and cerivastatin lactone, 0.0500 to 10.0 ng/ml for M-1 (acid) and M-1 lactone, 0.100 to 10.0 ng/ml for M-23 (acid) and M-23 lactone, and 0.500 to 10.0 ng/ml for M-24 (acid) and M-24 lactone. The lactone compounds in human serum at room temperature underwent considerable conversion to the corresponding acid compounds after only 4 h. Lowering the serum pH with a pH 5.0 buffer stabilized the lactone compounds for up to 24 h at room temperature. The degree of lactonization of the acid compounds was < or = 3.5% and the degree of hydrolysis of the lactone compounds was < or = 6.0% during the entire assay procedure. All the eight analytes eluted within 2.0 min and the total run time was only 3.5 min.

MeSH terms

  • Biotransformation
  • Chromatography, High Pressure Liquid / methods*
  • Drug Stability
  • Humans
  • Hydrogen-Ion Concentration
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Lactones / blood*
  • Mass Spectrometry / methods*
  • Pyridines / blood*
  • Pyridines / pharmacokinetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lactones
  • Pyridines
  • cerivastatin