Quality Assessment of Eicosapentanenoic Acid Ethyl Ester Formulations with Volatile Compound

Abstract

Eicosapentanenoic acid ethyl ester (EPA-E) formulation is a drug derived from fish oil. Some EPA-E formulations have a special odor depending on the manufacturing process and the type of sardine raw materials used. This odor affects the compliance of some patients. In this study, we report our assessment of the odors in each EPA-E formulation with gas chromatography/mass spectrometry (GC/MS). We used 3 lots of an original drug and 5 generic EPA-E formulations. EPA-E formulations were incubated at 40℃ in the absence of light. We collected the volatiles for 24 h immediately and 7 days later. The collected volatiles that were ultrasonically extracted with dichloromethane were used as GC/MS samples. We estimated the components on the basis of the fragment pattern and peak retention time on GC/MS. We performed principal component analysis (PCA) by using the peak area and 2-dimensional mapping, and evaluated the results. There was no change in the appearance of any of the formulations at 7 days, compared at the beginning of the experiment. However, the GC/MS measurements revealed the presence of 1-heptadecanal and 1-eicosanal, which were presumed to be oxidation decomposition products, in some formulations. These products were predicted to be the source of odors, and their intensities increased after 7 days. This difference was observed in the score plot between the 6 formulations as a result of PCA. The odors due to the decomposition products may influence the compliance of patients, and a detailed examination will be required.

Fatty Acid Treatment with Pure Omega-3 Eicosapentaenoic Acid Ethyl Ester for Patients with Cardiovascular Diseases: Differences between Branded (EPADEL®) and Generic Products

“…These products may contain extra contaminants due to differences in the raw materials used or in the purification process. Jobu et al conducted an accelerated test using the branded and several generic versions of a highly purified EPA and found that the decomposition products from autoxidation during storage produced odors, which may influence the drug adherence [8]. This problem was significantly suppressed by preservation with nitrogen gas replacement.…”

“…EPA drugs are prescribed as branded (EPADEL ® : highly purified EPA ethyl ester) or generic products in Japan but no data exist regarding differences in the treatment outcomes between the products. Also, Jobu et al conducted an accelerated test using the branded and several generic versions of a highly purified EPA and found that the decomposition products from autoxidation during storage produced odors, which may influence the drug adherence [8]. Therefore, we investigated the differences in EPA, DHA, AA and the EPA/AA ratio through blood sampling six months after daily administration of EPADEL ® and a generic EPA product (released by a drug company) was initiated in patients with cardiovascular diseases.…”