Selective and Sensitive UHPLC Method for the Trace Analysis of Formaldehyde in Drug Substance Using Fused-core Column Technology and Detailed Pre-column Derivatization study

Background: Formaldehyde is a key intermediate/reagent in the synthesis of many significant pharmaceutical compounds. It is genotoxic as it interacts with the DNA, RNA and hence there is a pressing need to develop sensitive analytical methods for its trace level determination. Objective: The present study aims to develop a simple and robust Ultra-High-Performance Liquid Chromatographic (UHPLC) method for the trace level quantification of a carcinogen-formaldehyde, in pharmaceutical drug substance. Methods: This method was developed on a conventional pre-column derivatization technique with brady's reagent followed by fast analysis on fused core C-18 Ascentis Express (150 x 4.6 mm, 2.7 mu m) column using ultraviolet (UV) detection. Optimization of the derivatization reaction time was conducted in different pH conditions. The optimized analytical method was fully validated in accordance with the current International Conference on Harmonization (ICH) Q2 guidelines, which demonstrated the developed method to be fast, specific, linear, sensitive, repeatable, accurate and convenient for routine quality control. Results: The developed method was linear, accurate and precise in the concentration of 12.8 ng/mL to 510.7 ng/mL. The LOD and LOQ were found to be 3.8 ng/mL and 12.8 ng/mL, respectively. Conclusion: The developed UHPLC can be used effectively for trace level quantification of formaldehyde in drug substances or drug products.

Automated summary

The study developed a UHPLC method for the trace level quantification of formaldehyde in pharmaceutical drug substance, meeting the standards outlined in the ICH Q2 guidelines. This method proved to be linear, accurate, precise, and suitable for routine quality control.