Identification of Four Process-Related Impurities in the Bulk Drug Butalbital Using HPLC-UV Photodiode Array Detection, Particle Beam MS, and NMR

Abstract

During the production of bulk active pharmaceutical ingredients, many opportunities for the generation of impurities may arise. In cases such as this, the impurities often result from “primary” impurities in raw materials, which are carried through the manufacturing process. Since these primary sources often are similar to the raw material in which they occur, the net effect is generation of impurities which may have a highly similar structure to the finished product. Due to such a comparable structure many characteristics which permit analytical resolution, such as the partitioning, chromatographic retention, and spectral characteristics (to name a few) of the impurities are also similar to the finished product. Using a combination of analytical techniques, however, it is possible to accurately describe the impurities. This is often necessary in closely regulated industries such as pharmaceutical manufacturing, where generation of accurate impurity profile methodologies is critical to GLP compliance¹.

Key Words:

• Process Impurities, Impurity Profile Analyses
• HPLC
• Mass Spectrometry
• Nuclear Magnetic Resonance
• UV Photodiode Array
• Butalbital
• Barbituric Acids
• Cope Structure
• GMP at Bulk Pharmaceutical Manufacturing Facilities