Forced degradation behavior of epidepride and development of a stability-indicating method based on liquid chromatography-mass spectrometry

Wei Hsi Chen, Yu Yung Lin, Yu Chang, Kang Wei Chang, Yi Chih Shia, Kung Tien Liu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A reversed-phase high performance liquid chromatography (RP-HPLC) and LC-tandem mass spectrometry (LC-MS/MS) method was applied to study the forced degradation behavior and stability of epidepride. 123I radioisotope-labeled epidepride, ((-)-N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-iodo-2,3-dimethoxybenzamide) is a radio-tracer with a very high affinity for dopamine D2 receptors in the brain and has been used as an imaging agent for single-photon emission computed tomography (SPECT). HPLC studies were performed using 127I-epidepride (the non-radioactive compound), instead of 123I-epidepride, with an RP-18 column using a mobile phase consisting of methanol, acetonitrile, and ammonium acetate (pH 7.0, 10 mM). The eluent flow rate and the wavelength for HPLC detection were 0.5 mL/min and 210 nm, respectively. The ligand was exposed to acid (1 N HCl) and alkaline (1 N NaOH) media and was subjected to oxidative decomposition at room temperature using 3% H2O2 and to thermal decomposition at 50°C. After various reaction times (0.5, 1, 2, 8, and 24 h), the substances were investigated by HPLC and LC-MS/MS. While no decomposition products were observed after the acidic, alkaline, and thermal treatments, but over 80% of the initial amount of 127I-epidepride was oxidized within 24 h in the presence of H2O2. Only one major oxidation product with an m/z value of 435 was observed, in addition to the 127I-epidepride species (m/z 419). The product was characterized by LC-MS/MS fragmentation; based on the results, the deteriorated type and fragmentation pathways could be proposed for epidepride.

Original languageEnglish
Pages (from-to)248-256
Number of pages9
JournalJournal of Food and Drug Analysis
Volume22
Issue number2
DOIs
Publication statusPublished - Jun 1 2014
Externally publishedYes

Fingerprint

Liquid Chromatography
liquid chromatography
Mass Spectrometry
mass spectrometry
degradation
high performance liquid chromatography
High Pressure Liquid Chromatography
ammonium acetate
thermal degradation
reversed-phase high performance liquid chromatography
radionuclides
dopamine
computed tomography
methodology
radio
Hot Temperature
wavelengths
tracer techniques
ambient temperature
methanol

Keywords

  • Epidepride
  • Forced degradation
  • Stress testing

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

Cite this

Forced degradation behavior of epidepride and development of a stability-indicating method based on liquid chromatography-mass spectrometry. / Chen, Wei Hsi; Lin, Yu Yung; Chang, Yu; Chang, Kang Wei; Shia, Yi Chih; Liu, Kung Tien.

In: Journal of Food and Drug Analysis, Vol. 22, No. 2, 01.06.2014, p. 248-256.

Research output: Contribution to journalArticle

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abstract = "A reversed-phase high performance liquid chromatography (RP-HPLC) and LC-tandem mass spectrometry (LC-MS/MS) method was applied to study the forced degradation behavior and stability of epidepride. 123I radioisotope-labeled epidepride, ((-)-N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-iodo-2,3-dimethoxybenzamide) is a radio-tracer with a very high affinity for dopamine D2 receptors in the brain and has been used as an imaging agent for single-photon emission computed tomography (SPECT). HPLC studies were performed using 127I-epidepride (the non-radioactive compound), instead of 123I-epidepride, with an RP-18 column using a mobile phase consisting of methanol, acetonitrile, and ammonium acetate (pH 7.0, 10 mM). The eluent flow rate and the wavelength for HPLC detection were 0.5 mL/min and 210 nm, respectively. The ligand was exposed to acid (1 N HCl) and alkaline (1 N NaOH) media and was subjected to oxidative decomposition at room temperature using 3{\%} H2O2 and to thermal decomposition at 50°C. After various reaction times (0.5, 1, 2, 8, and 24 h), the substances were investigated by HPLC and LC-MS/MS. While no decomposition products were observed after the acidic, alkaline, and thermal treatments, but over 80{\%} of the initial amount of 127I-epidepride was oxidized within 24 h in the presence of H2O2. Only one major oxidation product with an m/z value of 435 was observed, in addition to the 127I-epidepride species (m/z 419). The product was characterized by LC-MS/MS fragmentation; based on the results, the deteriorated type and fragmentation pathways could be proposed for epidepride.",
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