Pediatric formulations and challenges beyond technological development: Identification and in silico qualification of impurities in 5 mg primaquine tablets

Abstract

The present paper outlines the crucial analytical procedure for registering primaquine 5 mg tablets for pediatric use. In order to meet regulatory guidelines, the impurities detected during the long-term stability study of the tablets were identified and qualified. A C18 column was used for stability indicating chromatographic separation. Chromatography was conducted using a binary mobile phase comprising TFA 0.05 % and ACN at a ratio of 78:22 v/v for mobile phase A, and ACN for mobile phase B, in a gradient mode, at a flow rate of 0.8 mL min-1 and the wavelength was monitored at 265 nm by DAD. The elution times for the degradation products that reached the identification limit at 24 months were 15.87 min and 19.46 min for DP-2 and DP-3 respectively. LC-HRMS analysis of DP-2 and DP-3 resulted in identifying a protonated molecule peak with m/z values of 517.32599 and 461.21567, respectively. Elemental compositions of DP-2 and DP-3 were C₃₀H₄₁O₂N₆ and C₂₆H₂₉N₄O₄, correspondingly. DP-2 safety was assessed via in silico analysis and qualified with a specification of 0.6 %. DP-3, although finding its full identity was not possible, it was assigned a conservative specification of 0.5 % for the drug product. Our research has emphasized the significance of analytical development in enabling the evaluation of drug product quality and safety in the submission dossier. These results underline the challenges of analytical development in drug product lifecycle.