Document Detail


Quantitation of cerivastatin and its seven acid and lactone biotransformation products in human serum by liquid chromatography-electrospray tandem mass spectrometry.
MedLine Citation:
PMID:  10676982     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
M Jemal; S Rao; I Salahudeen; B C Chen; R Kates
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of chromatography. B, Biomedical sciences and applications     Volume:  736     ISSN:  1387-2273     ISO Abbreviation:  J. Chromatogr. B Biomed. Sci. Appl.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-03-07     Completed Date:  2000-03-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9714109     Medline TA:  J Chromatogr B Biomed Sci Appl     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  19-41     Citation Subset:  IM    
Affiliation:
Bioanalytical Research, Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research, Institute, New Brunswick, NJ 08903-0191, USA. jemalm@bms.com
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MeSH Terms
Descriptor/Qualifier:
Biotransformation
Chromatography, High Pressure Liquid / methods*
Drug Stability
Humans
Hydrogen-Ion Concentration
Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood*,  pharmacokinetics
Lactones / blood*
Mass Spectrometry / methods*
Pyridines / blood*,  pharmacokinetics
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Lactones; 0/Pyridines; 0/cerivastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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