Determination of the optical purity of N-nitrosofenfluramine found in the Chinese slimming diet

Ari Nakadai, Hirofumi Inagaki, Masayasu Minami, Hideyo Takahashi, Rie Namme, Motoyasu Ohsawa, Shiro Ikegami

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

From 2001 to the summer of 2002, more than 800 cases of liver damage were reported in Japan among people taking Chinese diet aids. The Japanese Ministry of Health, Labor and Welfare has recently announced that N-nitrosofenfluramine was the hepatotoxic compound contained in the diet aids based on animal experiments performed by the National Institute of Health Sciences. Although N-nitrosofenfluramine is a derivative of fenfluramine, a previously used anti-obesity drug, neither pharmacologic nor toxicologic properties have been reported for N-nitroso fenfluramine. It should be noted that N-nitrosofenfluramine has two optical isomers, although it is not yet known which isomer damages the liver and other organs. The Japanese Ministry of Health, Labor and Welfare has not commented on this point. Pursuing this question, 10 types of Chinese slimming aid samples including those obtained from patients with fulminating hepatitis were analyzed by NMR, GC/MS, and a newly established HPLC method using a chiral separation column. It was found that the N-nitrosofenfluramine in all of the toxic diet aids was the (S)-isomer form. No (R)-isomer was detected. These results strongly suggest that the nitroso-compound in the diets must be prepared from pharmacologically active (S)-fenfluramine (dexfenfluramine). Thus the pharmacologic and toxicologic properties of each isomer should be investigated.

Original languageEnglish
Pages (from-to)805-809
Number of pages5
JournalYakugaku Zasshi
Volume123
Issue number9
DOIs
Publication statusPublished - 2003 Sep

Keywords

  • Anorectic drug
  • Chinese diet
  • Chiral
  • Fenfluramine
  • N-nitrosofenfluramine
  • Optical purity

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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