A stability-indicating LC–MS/MS method optimization for Pemetrexed through design of experiments: Identification and characterization of major oxidative degradation product

• Published in: Journal of pharmaceutical and biomedical analysis 2020-05, Vol.183, p.113150-113150, Article 113150
• Main Authors: S.T, Narenderan, J, Ramesh, B, Babu, S.N, Meyyanathan
• Format: Article
• Language: English
• Subjects: Acetates - chemistry; Acetonitriles - chemistry; Chromatography, High Pressure Liquid - methods; Degradation product; Design of experiments; Drug Stability; High-performance liquid chromatography; Oxidation-Reduction; Pemetrexed; Pemetrexed - chemistry; Reproducibility of Results; Stability study; Tandem mass spectrometry; Tandem Mass Spectrometry - methods
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2020.113150

•Pemetrexed is widely used in the treatment of lung cancer.•HPLC stability-indicating method was developed employing design of experiments.•Forced degradation study was carried out as per ICH Q1A (R2) guidelines.•Major oxidative degradation product was identified and characterized by LC- MS/MS. A stability-indicating high-performance liquid chromatography method for Pemetrexed bulk was developed and validated as per the ICH guidelines by employing design of experiments methodology equipped with Box–Behnken design. The separation of Pemetrexed and its oxidative degradation product was achieved in isocratic elution mode with Zorbax C18 column (150 mm x 4.6 mm x5 μm) using 10 mM ammonium acetate (pH 4.5 adjusted with acetic acid) and acetonitrile in the ratio of 50:50, v/v with a flow rate of 1.0 mL/min at detection wavelength of 223 nm. Tandem mass spectrometry method was adopted to identify and characterize the major oxidative degradation product. The results obtained indicate that the method is specific, linear, precise and accurate for the determination of Pemetrexed and characterization of degradation product.