title: Identification and control of metal-chelating chromatographic artifacts in the analysis of a malonohydrazide derivative drug compound.
abstract: Two unusual chromatographic artifact peaks were detected in the HPLC analysis for content of a malonohydrazide derivative drug and drug-related impurities. The artifacts were identified as the copper(II) chelating complexes with the drug compound and one of the process impurities. Our investigations suggested that built-up of Cu(2+) contamination in the HPLC system was the primary source for formation of the chelating artifacts. A rinse procedure using diluted EDTA solution was developed, and demonstrated to effectively purge trace level of heavy metals including Cu(2+) from the system, and therefore inhibited the formation of both chelates. Furthermore, the rinse was shown to introduce no detrimental impact on the response accuracy of the active drug compound and related impurities.
authors.affiliation: Product Development Group, Pharmaceutical Development, GlaxoSmithKline, USA.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Yang
authors.forename: Anna
authors.initials: A
authors.lastname: Caltabiano
authors.forename: Lianming
authors.initials: L
authors.lastname: Wu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shen
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Alireza
authors.initials: A
authors.lastname: Kord
authors.forename: Leon
authors.initials: L
authors.lastname: Zhou
mesh_terms: D016477:Artifacts; D002614:Chelating Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003300:Copper / Q000302:isolation & purification*; D004340:Drug Contamination; D004492:Edetic Acid / Q000494:pharmacology*; D006834:Hydrazines / Q000032:analysis*; D013854:Thioamides / Q000032:analysis*
chemical_list: D002614:Chelating Agents; C552096:GSK 842879A; D006834:Hydrazines; D013854:Thioamides; D003300:Copper; D004492:Edetic Acid