title: Quantitation of cerivastatin and its seven acid and lactone biotransformation products in human serum by liquid chromatography-electrospray tandem mass spectrometry.
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.
authors.affiliation: Bioanalytical Research, Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research, Institute, New Brunswick, NJ 08903-0191, USA. jemalm@bms.com
authors.forename: M
authors.initials: M
authors.lastname: Jemal
authors.forename: S
authors.initials: S
authors.lastname: Rao
authors.forename: I
authors.initials: I
authors.lastname: Salahudeen
authors.forename: B C
authors.initials: BC
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Kates
mesh_terms: D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D007783:Lactones / Q000097:blood*; D013058:Mass Spectrometry / Q000379:methods*; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; D011725:Pyridines; C086276:cerivastatin