Limited sample stability of chenodeoxycholic acid in pharmaceutical quality control

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry
• Metabolic Diseases

Background:

• Amsterdam UMC prepares chenodeoxycholic acid (CDCA) capsules for cerebrotendinous xanthomatosis.
• Routine quality control of CDCA revealed an unknown impurity during related substances testing.

Purpose of the Study:

• To investigate the cause of an unknown impurity detected during CDCA quality control.
• To assess the stability of CDCA sample solutions under various storage conditions.

Main Methods:

• European Pharmacopoeia (PhEur) high-pressure liquid chromatography with refractive index detection (HPLC-RI) method was employed.
• CDCA sample solutions in methanol R were stored at 5°C and 25°C for 0, 1, 3, and 7 days.
• Analysis focused on the detection and quantification of related substances.

Main Results:

• An unknown impurity emerged in CDCA samples stored for as little as 1 day.
• The impurity's concentration increased with extended storage time and higher temperatures (25°C vs. 5°C).
• These findings confirmed sample instability as the source of the impurity.

Conclusions:

• Chenodeoxycholic acid (CDCA) sample solutions exhibit instability, leading to the formation of unknown impurities.
• Accurate quality control testing for CDCA related substances requires the use of freshly prepared sample solutions.
• Adherence to stability recommendations ensures the integrity of pharmaceutical analysis for CDCA.