GRADIENT HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR DEGRADATION PRODUCTS OF ADINAZOLAM MESYLATE IN A SUSTAINED-RELEASE TABLET FORMULATION

A gradient high performance liquid chromatographic method was develope d to determine degradation products of adinazolam mesylate in a sustai ned release tablet formulation. Sample preparations were chromatograph ed on a YMC-Basic column using a formate buffer/acetonitrile gradient with absorbance detection at 254 nm. Adinazolam mesylate was found to degrade at high relative humidity and temperature to form a major prod uct, the 6-aminoquinoline analog, plus numerous other compounds. Five of these compounds were identified and their structures indicate that the solid-state degradation of adinazolam, in the presence of sufficie nt moisture, involves not only a hydrolytic mechanism, but also an oxi dative mechanism. Potential process impurities were resolved from the drug and degradation products. Recovery was near 100% over the 0.5 to 10% range for the major degradate (6-aminoquinoline) and over the 0.5 to 1% range for the other analytes. The method was applied to tablet s amples stressed at high relative humidity and temperature. The relativ e standard deviation of the assay for the 6-aminoquinoline was less th an 2% and less than 13% for the minor components. Calculated mass bala nces (sum of adinazolam plus degradation products in the degraded tabl et divided by the same sum in the undegraded tablet) were less than 10 0% and were dependent on the extent of degradation in the tablet. The average mass balance result obtained for samples that were an average of 9.5% degraded was 95.0 +/- 1.5%. It is possible that the decrease i n mass balance with increase in percent degradation may be explained b y the formation of many components at trace levels due to degradation by various permutations of hydrolytic and oxidative reaction pathways.