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

A method for the simultaneous quantitation of cerivastatin (acid) and its b iotransformation 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 h igh-performance liquid chromatography (LC) with positive ion electrospray t andem mass spectrometry (MS-MS) was developed and validated. The method inv olves extraction of cerivastatin and its biotransformation products from ac idified human serum (0.5 ml) using methyl tert.-butyl ether. The standard c urve 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 lacto ne, 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 ser um at room temperature underwent considerable conversion to the correspondi ng acid compounds after only 4 h. Lowering the serum pH with a pH 5.0 buffe r stabilized the lactone compounds for up to 24 h at room temperature. The degree of lactonization of the acid compounds was less than or equal to 3.5 % and the degree of hydrolysis of the lactone compounds was less than or eq ual to 6.0% during the entire assay procedure. All the eight analytes elute d within 2.0 min and the total run time was only 3.5 min. (C) 1999 Elsevier Science B.V. All rights reserved.