Analysis of a novel diagnostic marker for SLOS based on LC/ESI-MS/MS by ESI-enhanced deuterium labeling

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15435
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Tokyo University of Science
• Principal Investigator: Ogawa Shoujiro 東京理科大学, 薬学部薬学科, 講師 (30546271)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 誘導体化 / LC/ESI-MS/MS / モノヒドロキシ-7-デヒドロコレステロール / ステロール

Outline of Final Research Achievements

The purpose of this research was to find a novel diagnostic marker for SLOS in choresterol disorder. Furthermore, I have also developed a novel derivatization reagent for increasing assay sensitivity based on LC/ESI-MS/MS analysis. 24S-Hydroxy-7-dehydrocholesterol was synthesized from inexpensive bile acid analogue in more than 10 steps, and 4α- and 4-βhydroxy-7-dehydrocholesterol was obtained from cholesterol in several synthesis steps. Separately, serum of SLOS model rats prepared by ingestion of 7-dehydrocholesterol reductase inhibitor AY9944 was also obtained.
Peaks derived from 4α- and 4-β-hydroxy-7-dehydrocholesterol were clearly observed in the model rat serum as measured by LC/ESI-MS/MS, and these are expected as diagnostic markers for SLOS.

Free Research Field

分析科学

Academic Significance and Societal Importance of the Research Achievements

PAを指標とした誘導体化試薬のデザインを基に，より高い検出感度向上能を有する試薬を開発できたことで，少量の生体試料で臨床診断が可能となった．
また4α-及び4β-OH-7-DHCがSLOSの新規な診断マーカー候補化合物として見出されたことから，我々の誘導体化試薬とLC/ESI-MS/MSを組み合わせたモノヒドロキシ-7-DHCの分析を新生児血清 (あるいはより少量の乾燥露紙血など) 分析に応用すれば，早期の診断法開発への道が開かれるものと期待される．