Forced Degradation Study of Vonoprazan Fumarate by HPLC and Characterisation of Its Degradation Products Using LC-QTOF-MS/MS.

RATIONALE: Acid-related disorders, including gastro-oesophageal reflux disease (GERD), peptic ulcers and Helicobacter pylori infection, affect millions worldwide. Vonoprazan fumarate, a potassium-competitive acid blocker, provides rapid and sustained acid suppression. Understanding its degradation behaviour is essential for ensuring drug stability, supporting formulation development and guiding quality control.

METHODS

Vonoprazan fumarate was subjected to acidic and basic hydrolysis, oxidation, thermal and photolytic stress to evaluate its degradation behaviour. Degradation products were separated by reversed-phase high-performance liquid chromatography (HPLC) using a gradient program optimised for mobile-phase composition and flow rate, thereby enabling the chromatographic resolution of closely eluting degradation products. Structural characterisation was performed using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS) based on accurate-mass measurements and diagnostic MS/MS dissociation patterns. The method was validated for linearity, precision, accuracy, selectivity and robustness.

RESULTS

Nine degradation products were detected under stress conditions: Basic hydrolysis yielded degradation product (DP)-1 and DP-8; acidic stress produced DP-1, DP-2 and DP-4; oxidation generated DP-1, DP-2, DP-7 and DP-8; and photolysis formed DP-1 to DP-6, DP-8 and DP-9. Three degradation products exhibited identical protonated molecules and closely comparable MS/MS dissociation patterns to the parent drug but differed in chromatographic retention times, with their relative distribution varying in solution- and solid-state upon UV exposure.

CONCLUSIONS

This study provides a comprehensive evaluation of the forced degradation behaviour of vonoprazan fumarate by RP-HPLC and characterisation of its degradation products using LC-QTOF-MS/MS, providing insights into its degradation pathways and supporting stability assessment. Comparative solution- and solid-state photostability studies revealed distinct degradation profiles, providing further insight into the photodegradation behaviour of vonoprazan fumarate.