Quantitation of tolmetin by high-performance liquid chromatography and method validation

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis
• Chemical Kinetics

Background:

• Tolmetin (TLM) is a nonsteroidal anti-inflammatory drug (NSAID).
• Understanding drug degradation pathways is crucial for pharmaceutical stability and efficacy.
• Existing analytical methods may lack the sensitivity or specificity for comprehensive degradation studies.

Purpose of the Study:

• To develop and validate a robust high-performance liquid chromatographic (HPLC) assay method for tolmetin (TLM) degradation.
• To investigate the stability of TLM under various stress conditions: acidic, basic, and photoirradiation.
• To determine the degradation kinetics of TLM, particularly under photodegradation.

Main Methods:

• Development of an HPLC method using an Inertsil 5 ODS-3V column and UV detection at 254 nm.
• Validation of the method for system suitability, peak integrity, resolution, selectivity, and specificity.
• Forced degradation studies under acidic, basic, and photoirradiated conditions.
• Kinetic analysis of photodegradation in alcoholic solvents.

Main Results:

• The developed HPLC method demonstrated excellent selectivity, specificity, and suitability for stability measurements.
• Intra- and interday coefficients of variation were low (0.20-1.77% and 0.12-3.40%, respectively), with high recoveries (98.7-101.7%).
• Tolmetin exhibited increased reactivity under acidic and photoirradiated conditions, but remained stable in a basic medium.
• Photodegradation of TLM followed an apparent first-order reaction in alcoholic solvents.

Conclusions:

• A validated HPLC assay method provides a reliable tool for assessing tolmetin degradation.
• Tolmetin's stability profile indicates sensitivity to light and acidic environments, necessitating careful handling and storage.
• The kinetic data on photodegradation offers insights into its degradation mechanism, vital for formulation development.