Sensitive Spectrophotometric Method for the Determination of Permetrexed Disodium in Pure and Pharmaceutical Formulations

Two simple, sensitive, rapid and accurate spectrophotometric methods have been proposed for the assay of disodium N-[p-[2-[(2-amino-4,7 dihydro- 4-oxo-1H-pyrrolo[2,3- d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamate (permetrexed disodium) in pure and pharmaceutical formulations. These methods were based on the measurement of absorbance of tris (bipyridyl) iron (II) [Method A] and the diazocoupling of permetrexed disodium with diazotized p-nitro aniline (DPNA) in basic medium [Method B] at 522 and 508 nm, respectively. Reaction conditions have been optimized to obtain colored complexes of higher sensitivity and longer stability. The absorbance increased linearly with increase in concentrations of permetrexed disodium, which were corroborated by correlation coefficient values (0.9948 and 0.9928 in methods A and B, respectively). The complexes obeyed Beer’s law over the concentration range of 0.2 - 12 μgmL-1 and 0.5 - 10 μgmL-1 in method A and method B, respectively. The common excipients and additives did not interfere in their determination. The developed methods have been successfully applied for the assay of PRX in bulk samples and pharmaceutical formulations.