Development of a purity control strategy for pemetrexed disodium and validation of associated analytical methodology

•Pemetrexed sodium purity methods were developed and validated.•Information and structure of 13 main impurities for pemetrexed sodium are provided.•Conditions for the system suitability solutions in situ preparation are described.•The system suitability assures the main impurities resolution and identification.•Relative response factors were determined using HPLC-UV in tandem with CAD or in combination with NMR.

Stability-indicating reversed phase HPLC methods have been developed and validated for the determination of 13 potential process and degradation impurities in pemetrexed disodium drug substance (DS) and pemetrexed for injection drug product (DP). This paper describes the development of HPLC-UV impurity methods for drug substance and drug product. Relative response factors (RRF) have been determined using HPLC-UV in tandem with CAD or by NMR detection. Conditions for the generation of system suitability solutions are described and assure adequate chromatographic resolution and peak identification without the need for impurity reference standards. The methods were fully validated and demonstrated to have acceptable specificity, linearity, accuracy, repeatability, intermediate precision, detection/quantitation limit, and robustness.

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