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

Abstract

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. 123 I radioisotope-labeled epidepride, [(−)- N -{[(2 S )-1-ethylpyrrolidin-2-yl]methyl}-5-iodo-2,3-dimethoxybenzamide] is a radiotracer with a high affinity for dopamine D 2 receptors in the brain and has been used as an imaging agent for single-photon emission computed tomography. HPLC studies were performed using 127 I-epidepride (the nonradioactive compound), instead of 123 I-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% H 2 O 2 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 127 I-epidepride was oxidized within 24 hours in the presence of H 2 O 2 . Only one major oxidation product with an m/z value of 435 was observed, in addition to the 127 I-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.

Determination of Impurities and Degradation Products/Causes for <i>m</i>-Iodobenzylguanidine Using HPLC-Tandem Mass Spectrometry

“…Figure 10. It is supposed that oxidization occurs on the iodide to form a hydroxyiodonium species, which is similar to the oxidization behavior of epidepride [28].…”

Chemometrics Approaches in Forced Degradation Studies of Pharmaceutical Drugs

“…In general terms, forced degradation studies are processes that involve the degradation of drugs under extreme conditions to accelerate the yielding of degradation products. The information obtained from these studies are usually used to determine the chemical stability, pathways of degradation, to identify the degradation products, conditions of storage, self-life, excipient compatibility, and also allow the development of selective analytical methods [52,53,54].…”

Comprehensive Review on the Degradation Chemistry and Toxicity Studies of Functional Materials

“…The "ICH Q3A and Q3B Guidelines" have been established to monitor impurities. 3 These regulatory guidelines are mandatory for final approval of a functional material in biomedical applications. The results of these degradation studies performed as per the guidelines generated useful data for estimation of the degradation pathways, physicochemical stability, storage conditions, and shelf life for regulatory approval.…”

“…The results of these degradation studies performed as per the guidelines generated useful data for estimation of the degradation pathways, physicochemical stability, storage conditions, and shelf life for regulatory approval. 3,4 The prevalence of degradation byproducts, measurement of the degradation level, and the toxicity limit should be selective and well developed for routine analysis in the future. Forced degradation experiments are essential for commercial production of products which target the following points:…”