title: Development of a purity control strategy for pemetrexed disodium and validation of associated analytical methodology.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States. Electronic address: warner_anne_m@lilly.com.
authors.forename: Anne
authors.initials: A
authors.lastname: Warner
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States.
authors.forename: Irina
authors.initials: I
authors.lastname: Piraner
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Weimer
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: White
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control*; D004355:Drug Stability; D005971:Glutamates / Q000032:analysis* / Q000592:standards; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000592:standards; D057230:Limit of Detection; D015394:Molecular Structure; D000068437:Pemetrexed; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine
keywords: Impurity control; Method validation; Pemetrexed disodium; Relative response factor determination; System suitability