Abstract
Three historical phenobarbital-containing pharmaceutical preparations with an age of 36-57 years from the date of manufacture were analyzed. The analyzed preparations also differed in the type of dosage form: dragee, suppository, and solution.
The aim was to evaluate the long-term stability of phenobarbital, within the systematic program aimed at studying the stability and degradation of active pharmaceutical ingredients in decades-old pharmaceutical products. The substances contained in the analyzed preparations were identified by reverse-phase HPLC with UV and high-resolution mass spectrometric detection, capillary zone electrolysis, and head-space solid-phase microextraction followed by GC-MS.
The content of the main active ingredients was determined and compared with the values declared by the manufacturer. No degradation of phenobarbital was found in two preparations, dragée "Sedobelin" and suppository "Spasmoveralgin," so phenobarbital is stable in these preparations even after 36, respectively 43, years since the production of a preparation.
In contrast, two degradation products were identified in the 57-year-old solution "Sklerophyllin": pheneturide and 3-aminopentanoic acid. The originally declared amount of phenobarbital was found to decrease by 12.5%.
Thus, it is clear that phenobarbital is stable for many decades in solid dosage forms, whereas in liquid dosage forms it is partially degraded. In the second part of the work, ESI highresolution mass spectra of four selected substances were interpreted: phenobarbital, pheneturide, 3-aminopentanoic acid, and 3,4-methylenedioxymethamphetamine.
The latter substance was surprisingly found in the suppository "Spasmoveralgin," probably as a degradation product of ephedrine contained in the product.