A new validated stability-indicating gradient RP-HPLC method for the determination of pemetrexed disodium and its process related substances
Pemetrexed disodium is used for the treatment of malignant pleural mesothelioma and lung cancer. In the present study a simple stability indicating RP-HPLC method was developed and validated for the determination of Pemetrexed disodium. The process related substances such as Dimer-1 impurity, Dimer-2 impurity, N-Methyl Pemetrexed, Pemetrexed diethyl ester, Alanine derivative of Pemetrexed, DMF derivative of Pemetrexed, Acid intermediate, Oxidation impurity and D-isomer were separated on gradient mode and quantified. Forced degradation studies were performed to prove the specificity. Hypersil BDS C18 100 x 4.6mm, 3µm was used for the separation (at 27°C) with mobile phase mixture consisting of (0.02M sodium dihydrogen phosphate with 0.1% HCOOH and pH 3.8 with dilute sodium hydroxide): Acetonitrile (40:60 v/v) (pH 3.8) with a flow rate of 1.2 mL/min. Methanol: water (1:1) was used as diluent and the eluted compounds were monitored at 240 nm. 0.5-1500 µg/mL with linear regression equation y = 20588x - 9294.1 (R2=0.9999). The degradation products observed during the forced degradation studies were well resolved from the drug peak and proving that the method is a stability-indicating method. The method was validated as per ICH guidelines.
Keywords: Pemetrexed disodium, RP-HPLC, gradient mode, Related substances, Stability indicating, Validation.
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