Attempts have been taken to study stress degradation of tiemonium methylsulphate (TMS). Quantum mechanical approach was applied to investigate the structural information, protein binding affinity and pharmacokinetic properties of the TMS and degradation products. Forced degradation study revealed that TMS degraded significantly under acid hydrolysis and photolytic degradation conditions than basic, thermal or oxidative conditions. Density functional theory (DFT) with B3LYP/6-31G+ (d, p) has been employed to optimize the structures. Frontier molecular orbital features (HOMO-LUMO) gap, hardness, softness), dipole moment, atomic partial charge, electrostatic potential and thermodynamic properties (electronic energy, enthalpy, Gibb's free energy) are investigated for optimization of degradation products. Molecular docking has been performed against muscarinic acetylcholine receptor protein 5DSG to search the binding affinity and mode(s). ADMET calculation predicts that all the products are non-carcinogenic and safe for oral administration.

UPLC stability indicating method was developed for determining ketorolac tromethamine in its degradation study at different conditions. An isocratic mobile phase composition of 60:10:30 (v/v) containing CH3OH, CH3CN and 5mM NaH2PO4 and C18 column were used at a flow rate of 0.20 mL min-1. Satisfactory retention time was found 2.13±0.05 min at 320 nm when monitored by DAD detector. Forced degradation studies of ketorolac tromethamine was also performed at the following conditions: acid and basic hydrolysis, heat (50-70°C for 1 hr), photolytic (UV and sunlight for up to 3 hr), oxidation (3% hydrogen peroxide for 1 hr). Forced degradation study revealed that ketorolac degraded significantly under thermal conditions. In 1N acid and base hydrolysis, degradation was moderately significant and comparable. It was degraded marginally in 0.1N acid-base hydrolysis which was comparable to oxidative conditions. But in photolytic condition ketorolac shows insignificant degradation. Method was also applied to pharmaceutical formulation.