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Determination of Key Intermediates in Cholesterol and Bile Acid Biosynthesis by Stable Isotope Dilution Mass Spectrometry

Authors: Tadashi Yoshida, Akira Honda, Hiroshi Miyazaki and Yasushi Matsuzaki
Publication Date: 25 Mar 2008
Analytical Chemistry Insights 2008:3 45-60

Tadashi Yoshida1, Akira Honda2, Hiroshi Miyazaki3 and Yasushi Matsuzaki2

1Raffles Japanese Clinic, Singapore, Singapore. 2Tokyo Medical University, Kasumigaura Hospital, Ibaraki, Japan. 3Pharmax Institute, Kanagawa, Japan.

Abstract

For more than a decade, we have developed stable isotope dilution mass spectrometry methods to quantify key intermediates in cholesterol and bile acid biosynthesis, mevalonate and oxysterols, respectively. The methods are more sensitive and reproducible than conventional radioisotope (RI), gas-chromatography (GC) or high-performance liquid chromatography (HPLC) methods, so that they are applicable not only to samples from experimental animals but also to small amounts of human specimens. In this paper, we review the development of stable isotope dilution mass spectrometry for quantifying mevalonate and oxysterols in biological materials, and demonstrate the usefulness of this technique.