Forced degradation behavior of epidepride and development of a stability-indicating method based on liquid chromatography–mass spectrometry
2014
Chen, Wei-Hsi | Lin, Yu-Yung | Chang, Yu | Chang, Kang-Wei | Hsia, Yi-Chih
A reversed-phase high-performance liquid chromatography (HPLC) and liquid chromatography-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 radiotracer with a high affinity for dopamine D2 receptors in the brain and has been used as an imaging agent for single-photon emission computed tomography. HPLC studies were performed using 127I-epidepride (the nonradioactive 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 (30 minutes, 1 hour, 2 hours, 8 hours, and 24 hours), the substances were investigated by HPLC and LC-MS/MS. Although no decomposition products were observed after the acidic, alkaline, and thermal treatments, >80% of the initial amount of 127I-epidepride was oxidized within 24 hours 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, and the deteriorated type and fragmentation pathways were proposed for epidepride.
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